{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T22:37:34Z","timestamp":1775515054935,"version":"3.50.1"},"reference-count":147,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T00:00:00Z","timestamp":1693008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["K08DE031039"],"award-info":[{"award-number":["K08DE031039"]}]},{"name":"Van Andel Institute","award":["K08DE031039"],"award-info":[{"award-number":["K08DE031039"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The ability to create genetically engineered mouse models (GEMMs) has exponentially increased our understanding of many areas of biology. Musculoskeletal biology is no exception. In this review, we will first discuss the historical development of GEMMs and how these developments have influenced musculoskeletal disease research. This review will also update our 2008 review that appeared in BONEKey, a journal that is no longer readily available online. We will first review the historical development of GEMMs in general, followed by a particular emphasis on the ability to perform tissue-specific (conditional) knockouts focusing on musculoskeletal tissues. We will then discuss how the development of CRISPR\/Cas-based technologies during the last decade has revolutionized the generation of GEMMs.<\/jats:p>","DOI":"10.3390\/biom13091311","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T01:56:57Z","timestamp":1693187817000},"page":"1311","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Past, Present, and Future of Genetically Engineered Mouse Models for Skeletal Biology"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2253-3919","authenticated-orcid":false,"given":"Megan N.","family":"Michalski","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Van Andel Institute, Grand Rapids, MI 49503, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart O.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Van Andel Institute, Grand Rapids, MI 49503, USA"},{"name":"Core Technologies and Services, Van Andel Institute, Grand Rapids, MI 49503, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ydbio.2015.07.023","article-title":"Discovery and characterization of spontaneous mouse models of craniofacial dysmorphology","volume":"415","author":"Palmer","year":"2016","journal-title":"Dev. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1101\/gr.186882.114","article-title":"Exome sequencing reveals pathogenic mutations in 91 strains of mice with Mendelian disorders","volume":"25","author":"Fairfield","year":"2015","journal-title":"Genome Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"934","DOI":"10.3389\/fendo.2019.00934","article-title":"High Fidelity of Mouse Models Mimicking Human Genetic Skeletal Disorders","volume":"10","author":"Brommage","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1002\/jbmr.4323","article-title":"Germline Saturation Mutagenesis Induces Skeletal Phenotypes in Mice","volume":"36","author":"Rios","year":"2021","journal-title":"J. Bone Miner Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1073\/pnas.71.4.1250","article-title":"Simian Virus 40 DNA Sequences in DNA of Healthy Adult Mice Derived from Preimplantation Blastocysts Injected with Viral DNA","volume":"71","author":"Jaenisch","year":"1974","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","unstructured":"National Research Council (1994). Sharing Laboratory Resources: Genetically Altered Mice: Summary of a Workshop Held at the National Academy of Sciences, 23\u201324 March 1993, National Research Council."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7380","DOI":"10.1073\/pnas.77.12.7380","article-title":"Genetic transformation of mouse embryos by microinjection of purified DNA","volume":"77","author":"Gordon","year":"1980","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/292154a0","article-title":"Establishment in culture of pluripotential cells from mouse embryos","volume":"292","author":"Evans","year":"1981","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7634","DOI":"10.1073\/pnas.78.12.7634","article-title":"Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells","volume":"78","author":"Martin","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/309255a0","article-title":"Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines","volume":"309","author":"Bradley","year":"1984","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/nm1001-1083","article-title":"Forty years with homologous recombination","volume":"7","author":"Smithies","year":"2001","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/0092-8674(91)90499-O","article-title":"Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice","volume":"64","author":"Soriano","year":"1991","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0168-9525(00)89008-3","article-title":"Death before birth: Clues from gene knockouts and mutations","volume":"11","author":"Copp","year":"1995","journal-title":"Trends Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/0022-2836(84)90154-2","article-title":"Site-specific recombination by the bacteriophage P1 lox-Cre system: Cre-mediated synapsis of two lox sites","volume":"178","author":"Hamilton","year":"1984","journal-title":"J. Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/(SICI)1526-968X(200002)26:2<99::AID-GENE1>3.0.CO;2-B","article-title":"Cre recombinase: The universal reagent for genome tailoring","volume":"26","author":"Nagy","year":"2000","journal-title":"Genesis"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5166","DOI":"10.1073\/pnas.85.14.5166","article-title":"Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1","volume":"85","author":"Sauer","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/nar\/17.1.147","article-title":"Cre-stimulated recombination at loxP-containing DNA sequences placed into the mammalian genome","volume":"17","author":"Sauer","year":"1989","journal-title":"Nucleic Acids Res."},{"key":"ref_18","first-page":"441","article-title":"Targeted insertion of exogenous DNA into the eukaryotic genome by the Cre recombinase","volume":"2","author":"Sauer","year":"1990","journal-title":"New Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6232","DOI":"10.1073\/pnas.89.14.6232","article-title":"Targeted oncogene activation by site-specific recombination in transgenic mice","volume":"89","author":"Lakso","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6861","DOI":"10.1073\/pnas.89.15.6861","article-title":"Tissue- and site-specific DNA recombination in transgenic mice","volume":"89","author":"Orban","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"147","DOI":"10.5625\/lar.2018.34.4.147","article-title":"Mouse Cre-LoxP system: General principles to determine tissue-specific roles of target genes","volume":"34","author":"Kim","year":"2018","journal-title":"Lab. Anim. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/nature01657","article-title":"Developmental regulation of the growth plate","volume":"423","author":"Kronenberg","year":"2003","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1002\/dvdy.278","article-title":"Making and shaping endochondral and intramembranous bones","volume":"250","author":"Galea","year":"2020","journal-title":"Dev. Dyn."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s11914-007-0007-z","article-title":"The biology of osteocytes","volume":"5","author":"Kogianni","year":"2007","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1002\/jcb.21553","article-title":"The osteoclast: A multinucleated, hematopoietic-origin, bone-resorbing osteoimmune cell","volume":"102","year":"2007","journal-title":"J. Cell. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s12325-021-01936-y","article-title":"Denosumab in the Treatment of Osteoporosis: 10 Years Later: A Narrative Review","volume":"39","author":"Kendler","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nrd3705","article-title":"Bench to bedside: Elucidation of the OPG\u2013RANK\u2013RANKL pathway and the development of denosumab","volume":"11","author":"Lacey","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0092-8674(00)80209-3","article-title":"Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density","volume":"89","author":"Simonet","year":"1997","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1138\/20080312","article-title":"Transgenic mouse strains for conditional gene deletion during skeletal development","volume":"5","author":"VanKoevering","year":"2008","journal-title":"IBMS BoneKEy"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.cell.2004.07.023","article-title":"Dynamic Changes in the Response of Cells to Positive Hedgehog Signaling during Mouse Limb Patterning","volume":"118","author":"Ahn","year":"2004","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1038\/s41467-017-02171-2","article-title":"Gli1 identifies osteogenic progenitors for bone formation and fracture repair","volume":"8","author":"Shi","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.cell.2014.11.042","article-title":"Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential","volume":"160","author":"Worthley","year":"2015","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2608","DOI":"10.1126\/science.1056602","article-title":"Virus-Assisted Mapping of Neural Inputs to a Feeding Center in the Hypothalamus","volume":"291","author":"DeFalco","year":"2001","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.stem.2014.06.008","article-title":"Faculty Opinions recommendation of Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow","volume":"15","author":"Zhou","year":"2014","journal-title":"Cell Stem Cell"},{"key":"ref_35","first-page":"386","article-title":"The suture provides a niche for mesenchymal stem cells of craniofacial bones","volume":"17","author":"Zhao","year":"2015","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1242\/dev.115.4.1045","article-title":"Platelet-derived growth factor-A and its receptor are expressed in separate, but adjacent cell layers of the mouse embryo","volume":"115","author":"Lonai","year":"1992","journal-title":"Development"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1038\/nn.2220","article-title":"PDGFRA\/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice","volume":"11","author":"Rivers","year":"2008","journal-title":"Nat. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.neuron.2010.09.009","article-title":"NG2+ CNS Glial Progenitors Remain Committed to the Oligodendrocyte Lineage in Postnatal Life and following Neurodegeneration","volume":"68","author":"Kang","year":"2010","journal-title":"Neuron"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/dvdy.21","article-title":"The platelet-derived growth factor receptor alpha promoter-directed expression of cre recombinase in mouse placenta","volume":"248","author":"Wattez","year":"2019","journal-title":"Dev. Dyn."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"O\u2019Rourke, M., Cullen, C.L., Auderset, L., Pitman, K.A., Achatz, D., Gasperini, R., and Young, K.M. (2016). Evaluating Tissue-Specific Recombination in a Pdgfralpha-CreERT2 Transgenic Mouse Line. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162858"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41413-021-00176-8","article-title":"PDGFRalpha reporter activity identifies periosteal progenitor cells critical for bone formation and fracture repair","volume":"10","author":"Xu","year":"2022","journal-title":"Bone Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"dev179325","DOI":"10.1242\/dev.179325","article-title":"Skeletal stem cells: Insights into maintaining and regenerating the skeleton","volume":"147","author":"Serowoky","year":"2020","journal-title":"Development"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/stem.780","article-title":"In Vivo Fate Mapping Identifies Mesenchymal Progenitor Cells","volume":"30","author":"Grcevic","year":"2012","journal-title":"Stem Cells"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41467-019-14029-w","article-title":"A Wnt-mediated transformation of the bone marrow stromal cell identity orchestrates skeletal regeneration","volume":"11","author":"Matsushita","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1126\/science.7660125","article-title":"Inducible Gene Targeting in Mice","volume":"269","author":"Schwenk","year":"1995","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14248","DOI":"10.1523\/JNEUROSCI.4531-07.2007","article-title":"Mosaic Removal of Hedgehog Signaling in the Adult SVZ Reveals That the Residual Wild-Type Stem Cells Have a Limited Capacity for Self-Renewal","volume":"27","author":"Balordi","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/gene.10092","article-title":"Expression of Cre recombinase in the developing mouse limb bud driven by aPrxl enhancer","volume":"33","author":"Logan","year":"2002","journal-title":"Genesis"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.bbrc.2009.06.059","article-title":"Mice expressing GFP and CreER in osteochondro progenitor cells in the periosteum","volume":"386","author":"Kawanami","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1006\/dbio.1995.0023","article-title":"Dermo-1: A Novel Twist-Related bHLH Protein Expressed in the Developing Dermis","volume":"172","author":"Li","year":"1995","journal-title":"Dev. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1242\/dev.00491","article-title":"Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in the regulation of osteoblast function and bone growth","volume":"130","author":"Yu","year":"2003","journal-title":"Development"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/5007","article-title":"Generalized lacZ expression with the ROSA26 Cre reporter strain","volume":"21","author":"Soriano","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"De Langhe, S.P., Carraro, G., Tefft, D., Li, C., Xu, X., Chai, Y., Minoo, P., Hajihosseini, M.K., Drouin, J., and Kaartinen, V. (2008). Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001516"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1183\/09031936.00165407","article-title":"TGF-{beta} receptor II in Epithelia Versus Mesenchyme Plays Distinct Role in Developing Lung","volume":"32","author":"Chen","year":"2008","journal-title":"Eur. Respir. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"10738","DOI":"10.1074\/jbc.275.15.10738","article-title":"SOX9 Enhances Aggrecan Gene Promoter\/Enhancer Activity and Is Up-regulated by Retinoic Acid in a Cartilage-derived Cell Line, TC6","volume":"275","author":"Sekiya","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1128\/MCB.17.4.2336","article-title":"SOX9 is a potent activator of the chondrocyte-specific enhancer of the pro alpha1(II) collagen gene","volume":"17","author":"Lefebvre","year":"1997","journal-title":"Mol. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"14998","DOI":"10.1074\/jbc.273.24.14998","article-title":"Chondrocyte-specific Enhancer Elements in the Col11a2 Gene Resemble the Col2a1 Tissue-specific Enhancer","volume":"273","author":"Bridgewater","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1006\/dbio.1996.8487","article-title":"SOX9 Binds DNA, Activates Transcription, and Coexpresses with Type II Collagen during Chondrogenesis in the Mouse","volume":"183","author":"Ng","year":"1997","journal-title":"Dev. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"14665","DOI":"10.1073\/pnas.0504750102","article-title":"Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors","volume":"102","author":"Akiyama","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/(SICI)1526-968X(200002)26:2<145::AID-GENE14>3.0.CO;2-C","article-title":"Col2a1-directed expression of Cre recombinase in differentiating chondrocytes in transgenic mice","volume":"26","author":"Ovchinnikov","year":"2000","journal-title":"Genesis"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5099","DOI":"10.1242\/dev.128.24.5099","article-title":"Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation","volume":"128","author":"Long","year":"2001","journal-title":"Development"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1101\/gad.934301","article-title":"Hypoxia in cartilage: HIF-1\u03b1 is essential for chondrocyte growth arrest and survival","volume":"15","author":"Schipani","year":"2001","journal-title":"Genes Dev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/S0945-053X(00)00122-0","article-title":"Stage-and tissue-specific expression of a Col2a1-Cre fusion gene in transgenic mice","volume":"19","author":"Sakai","year":"2001","journal-title":"Matrix Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1083\/jcb.200302066","article-title":"Reduced chondrocyte proliferation and chondrodysplasia in mice lacking the integrin-linked kinase in chondrocytes","volume":"162","author":"Terpstra","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1242\/dev.127.7.1445","article-title":"Conditional inactivation of VEGF-A in areas of collagen2a1 expression results in embryonic lethality in the heterozygous state","volume":"127","author":"Haigh","year":"2000","journal-title":"Development"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1002\/dvdy.20892","article-title":"Kinetics of tamoxifen-regulated Cre activity in mice using a cartilage-specific CreER(T) to assay temporal activity windows along the proximodistal limb skeleton","volume":"235","author":"Nakamura","year":"2006","journal-title":"Dev. Dyn."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.matbio.2005.11.003","article-title":"Generation of a transgenic mouse in which Cre recombinase is expressed under control of the type II collagen promoter and doxycycline administration","volume":"25","author":"Grover","year":"2006","journal-title":"Matrix Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/dvg.20261","article-title":"Generation of a transgenic mouse model with chondrocyte-specific and tamoxifen-inducible expression of Cre recombinase","volume":"45","author":"Chen","year":"2007","journal-title":"Genesis"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ydbio.2007.05.011","article-title":"Tamoxifen-inducible gene deletion reveals a distinct cell type associated with trabecular bone, and direct regulation of PTHrP expression and chondrocyte morphology by Ihh in growth region cartilage","volume":"308","author":"Hilton","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1002\/jbmr.4415","article-title":"Sites of Cre-recombinase activity in mouse lines targeting skeletal cells","volume":"36","author":"Couasnay","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/gene.20120","article-title":"Transgenic mice that express Cre recombinase in hypertrophic chondrocytes","volume":"42","author":"Yang","year":"2005","journal-title":"Genesis"},{"key":"ref_71","first-page":"123","article-title":"Generation of transgenic mice for conditional overexpression of Sox9","volume":"29","author":"Kim","year":"2010","journal-title":"J. Bone Miner. Metab."},{"key":"ref_72","first-page":"6672","article-title":"Hypertrophic chondrocyte-specific Col10a1 controlling elements in Cre recombinase transgenic studies","volume":"11","author":"Chen","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.matbio.2008.07.001","article-title":"Specific expression of Cre recombinase in hypertrophic cartilage under the control of a BAC-Col10a1 promoter","volume":"27","author":"Gebhard","year":"2008","journal-title":"Matrix Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"12097","DOI":"10.1073\/pnas.1302703111","article-title":"Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation","volume":"111","author":"Yang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1002\/dvg.20564","article-title":"Generation of aggrecan-CreERT2 knockin mice for inducible Cre activity in adult cartilage","volume":"47","author":"Henry","year":"2009","journal-title":"Genesis"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"15040","DOI":"10.1038\/ncomms15040","article-title":"Joint morphogenetic cells in the adult mammalian synovium","volume":"8","author":"Roelofs","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Rountree, R.B., Schoor, M., Chen, H., Marks, M.E., Harley, V., Mishina, Y., and Kingsley, D.M. (2004). BMP Receptor Signaling Is Required for Postnatal Maintenance of Articular Cartilage. PLoS Biol., 2.","DOI":"10.1371\/journal.pbio.0020355"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1016\/j.celrep.2016.05.055","article-title":"Faculty Opinions recommendation of Joint Development Involves a Continuous Influx of Gdf5-Positive Cells","volume":"15","author":"Shwartz","year":"2016","journal-title":"Cell Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ydbio.2017.04.006","article-title":"Cell origin, volume and arrangement are drivers of articular cartilage formation, morphogenesis and response to injury in mouse limbs","volume":"426","author":"Decker","year":"2017","journal-title":"Dev. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1002\/art.39030","article-title":"Identification of a Prg4-Expressing Articular Cartilage Progenitor Cell Population in Mice","volume":"67","author":"Kozhemyakina","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/s41586-018-0662-5","article-title":"Resting zone of the growth plate houses a unique class of skeletal stem cells","volume":"563","author":"Mizuhashi","year":"2018","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1210\/endo.142.7.8306","article-title":"Minireview: Transcriptional control of osteoblast differentiation","volume":"142","author":"Karsenty","year":"2001","journal-title":"Endocrinology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.cmet.2010.05.005","article-title":"Glucocorticoids Suppress Bone Formation by Attenuating Osteoblast Differentiation via the Monomeric Glucocorticoid Receptor","volume":"11","author":"Rauch","year":"2010","journal-title":"Cell Metab."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1242\/dev.02480","article-title":"Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors","volume":"133","author":"Rodda","year":"2006","journal-title":"Development"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.devcel.2010.07.010","article-title":"Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels","volume":"19","author":"Maes","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1073\/pnas.93.3.1027","article-title":"Identification of a minimal sequence of the mouse pro-alpha 1(I) collagen promoter that confers high-level osteoblast expression in transgenic mice and that binds a protein selectively present in osteoblasts","volume":"93","author":"Rossert","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1083\/jcb.129.5.1421","article-title":"Separate cis-acting DNA elements of the mouse pro-alpha 1(I) collagen promoter direct expression of reporter genes to different type I collagen-producing cells in transgenic mice","volume":"129","author":"Rossert","year":"1995","journal-title":"J. Cell Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/dvdy.10100","article-title":"Mouse \u03b11(I)-collagen promoter is the best known promoter to drive efficient Cre recombinase expression in osteoblast","volume":"224","author":"Dacquin","year":"2002","journal-title":"Dev. Dyn."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1387\/ijdb.041816fl","article-title":"Expression and activity of osteoblast-targeted Cre recombinase transgenes in murine skeletal tissues","volume":"48","author":"Liu","year":"2004","journal-title":"Int. J. Dev. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S1673-8527(08)60072-7","article-title":"Collagen1\u03b11 promoter drives the expression of Cre recombinase in osteoblasts of transgenic mice","volume":"35","author":"Zha","year":"2008","journal-title":"J. Genet. Genom."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1016\/S0002-9440(10)63240-3","article-title":"Transgenic Mice Expressing a Ligand-Inducible Cre Recombinase in Osteoblasts and Odontoblasts: A New Tool to Examine Physiology and Disease of Postnatal Bone and Tooth","volume":"165","author":"Kim","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"44005","DOI":"10.1074\/jbc.M208265200","article-title":"Osteoblast-specific Knockout of the Insulin-like Growth Factor (IGF) Receptor Gene Reveals an Essential Role of IGF Signaling in Bone Matrix Mineralization","volume":"277","author":"Zhang","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1002\/jbmr.417","article-title":"Genetic evidence points to an osteocalcin-independent influence of osteoblasts on energy metabolism","volume":"26","author":"Yoshikawa","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1152\/physrev.00043.2020","article-title":"The osteocyte as a signaling cell","volume":"102","author":"Bellido","year":"2022","journal-title":"Physiol. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"116087","DOI":"10.1016\/j.bone.2021.116087","article-title":"The Wnt pathway: An important control mechanism in bone\u2019s response to mechanical loading","volume":"153","author":"Choi","year":"2021","journal-title":"Bone"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1615\/CritRevEukarGeneExpr.v19.i4.50","article-title":"Mechanical Signaling for Bone Modeling and Remodeling","volume":"19","author":"Robling","year":"2009","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1038\/nm.2452","article-title":"Evidence for osteocyte regulation of bone homeostasis through RANKL expression","volume":"17","author":"Nakashima","year":"2011","journal-title":"Nat. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1038\/nm.2448","article-title":"Matrix-embedded cells control osteoclast formation","volume":"17","author":"Xiong","year":"2011","journal-title":"Nat. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"23698","DOI":"10.1074\/jbc.M601000200","article-title":"The Wnt Co-receptor LRP5 Is Essential for Skeletal Mechanotransduction but Not for the Anabolic Bone Response to Parathyroid Hormone Treatment","volume":"281","author":"Sawakami","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1177\/154405910708600404","article-title":"DMP1-targeted Cre Expression in Odontoblasts and Osteocytes","volume":"86","author":"Lu","year":"2007","journal-title":"J. Dent. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.bone.2004.03.006","article-title":"Dentin matrix protein 1 expression during osteoblastic differentiation, generation of an osteocyte GFP-transgene","volume":"35","author":"Kalajzic","year":"2004","journal-title":"Bone"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"16049","DOI":"10.1038\/boneres.2016.49","article-title":"Unintended targeting of Dmp1-Cre reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice","volume":"5","author":"Lim","year":"2017","journal-title":"Bone Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/jbmr.548","article-title":"Cell autonomous requirement of connexin 43 for osteocyte survival: Consequences for endocortical resorption and periosteal bone formation","volume":"27","author":"Bivi","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1530\/JOE-10-0308","article-title":"Targeted ablation of the PTH\/PTHrP receptor in osteocytes impairs bone structure and homeostatic calcemic responses","volume":"209","author":"Powell","year":"2011","journal-title":"J. Endocrinol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1084\/jem.20031454","article-title":"Sclerostin Is an Osteocyte-expressed Negative Regulator of Bone Formation, But Not a Classical BMP Antagonist","volume":"199","author":"Roelen","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Xiong, J., Piemontese, M., Onal, M., Campbell, J., Goellner, J.J., Dusevich, V., Bonewald, L., Manolagas, S.C., and O\u2019brien, C.A. (2015). Osteocytes, not Osteoblasts or Lining Cells, are the Main Source of the RANKL Required for Osteoclast Formation in Remodeling Bone. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138189"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41413-018-0037-4","article-title":"Characterization of a novel murine Sost ER(T2) Cre model targeting osteocytes","volume":"7","author":"Maurel","year":"2019","journal-title":"Bone Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"952","DOI":"10.2353\/ajpath.2010.090622","article-title":"A Novel Mouse Model of Inflammatory Bowel Disease Links Mammalian Target of Rapamycin-Dependent Hyperproliferation of Colonic Epithelium to Inflammation-Associated Tumorigenesis","volume":"176","author":"Deng","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nature10138","article-title":"CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis","volume":"475","author":"Qian","year":"2011","journal-title":"Nature"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1023\/A:1008942828960","article-title":"Conditional gene targeting in macrophages and granulocytes using LysMcre mice","volume":"8","author":"Clausen","year":"1999","journal-title":"Transgenic Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1002\/gene.20108","article-title":"Targeted expression of Cre recombinase in macrophages and osteoclasts in transgenic mice","volume":"41","author":"Ferron","year":"2005","journal-title":"Genesis"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1002\/gene.20041","article-title":"Transgenic mice that express Cre recombinase in osteoclasts","volume":"39","author":"Chiu","year":"2004","journal-title":"Genesis"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1080\/08916930701694667","article-title":"Tartrate-resistant acid phosphatase (TRAP) and the osteoclast\/immune cell dichotomy","volume":"41","author":"Hayman","year":"2008","journal-title":"Autoimmunity"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.biochi.2007.08.011","article-title":"Biochemical properties and regulation of cathepsin K activity","volume":"90","author":"Lecaille","year":"2008","journal-title":"Biochimie"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1002\/jcb.22609","article-title":"Osteoclast-specific inactivation of the integrin-linked kinase (ILK) inhibits bone resorption","volume":"110","author":"Dossa","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/35093556","article-title":"Recombineering: A powerful new tool for mouse functional genomics","volume":"2","author":"Copeland","year":"2001","journal-title":"Nat. Rev. Genet."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.cell.2007.07.025","article-title":"Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts","volume":"130","author":"Nakamura","year":"2007","journal-title":"Cell"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Sanchez-Fernandez, M.A., Sbacchi, S., Correa-Tapia, M., Naumann, R., Klemm, J., Chambon, P., Al-Robaiy, S., Blessing, M., and Hoflack, B. (2012). Transgenic Mice for a Tamoxifen-Induced, Conditional Expression of the Cre Recombinase in Osteoclasts. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037592"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.cell.2013.04.025","article-title":"One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR\/Cas-Mediated Genome Engineering","volume":"153","author":"Wang","year":"2013","journal-title":"Cell"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1126\/science.1231143","article-title":"Multiplex Genome Engineering Using CRISPR\/Cas Systems","volume":"339","author":"Cong","year":"2013","journal-title":"Science"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.cell.2013.02.022","article-title":"Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression","volume":"152","author":"Qi","year":"2013","journal-title":"Cell"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/nmeth.2649","article-title":"Cas9 as a versatile tool for engineering biology","volume":"10","author":"Mali","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/nbt.2675","article-title":"CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering","volume":"31","author":"Mali","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.1225829","article-title":"A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity","volume":"337","author":"Jinek","year":"2012","journal-title":"Science"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"24356","DOI":"10.1038\/srep24356","article-title":"CRISPR-Cas9(D10A) nickase-based genotypic and phenotypic screening to enhance genome editing","volume":"6","author":"Chiang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/nature17946","article-title":"Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage","volume":"533","author":"Komor","year":"2016","journal-title":"Nature"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/nature24644","article-title":"Programmable base editing of A\u2022T to G\u2022C in genomic DNA without DNA cleavage","volume":"551","author":"Gaudelli","year":"2017","journal-title":"Nature"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41587-020-0609-x","article-title":"CRISPR C-to-G base editors for inducing targeted DNA transversions in human cells","volume":"39","author":"Kurt","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/s41586-019-1711-4","article-title":"Search-and-replace genome editing without double-strand breaks or donor DNA","volume":"576","author":"Anzalone","year":"2019","journal-title":"Nature"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1038\/s41596-019-0187-x","article-title":"Creation of CRISPR-based germline-genome-engineered mice without ex vivo handling of zygotes by i-GONAD","volume":"14","author":"Gurumurthy","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-018-1400-x","article-title":"i-GONAD: A robust method for in situ germline genome engineering using CRISPR nucleases","volume":"19","author":"Ohtsuka","year":"2018","journal-title":"Genome Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"jkab194","DOI":"10.1093\/g3journal\/jkab194","article-title":"An efficient i-GONAD method for creating and maintaining lethal mutant mice using an inversion balancer identified from the C3H\/HeJJcl strain","volume":"11","author":"Iwata","year":"2021","journal-title":"G3 Genes Genomes Genet."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/dgd.12746","article-title":"GONAD: A new method for germline genome editing in mice and rats","volume":"63","author":"Namba","year":"2021","journal-title":"Dev. Growth Differ."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00441-021-03450-7","article-title":"Functional validation of epitope-tagged ATF5 knock-in mice generated by improved genome editing of oviductal nucleic acid delivery (i-GONAD)","volume":"385","author":"Nakano","year":"2021","journal-title":"Cell Tissue Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1101\/gr.265439.120","article-title":"Generation of mouse conditional knockout alleles in one step using the i-GONAD method","volume":"31","author":"Shang","year":"2020","journal-title":"Genome Res."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Kobayashi, Y., Aoshima, T., Ito, R., Shinmura, R., Ohtsuka, M., Akasaka, E., Sato, M., and Takabayashi, S. (2020). Modification of i-GONAD Suitable for Production of Genome-Edited C57BL\/6 Inbred Mouse Strain. Cells, 9.","DOI":"10.3390\/cells9040957"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Sato, M., Takabayashi, S., Akasaka, E., and Nakamura, S. (2020). Recent Advances and Future Perspectives of In Vivo Targeted Delivery of Genome-Editing Reagents to Germ cells, Embryos, and Fetuses in Mice. Cells, 9.","DOI":"10.3390\/cells9040799"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Sato, M., Miyagasako, R., Takabayashi, S., Ohtsuka, M., Hatada, I., and Horii, T. (2020). Sequential i-GONAD: An Improved In Vivo Technique for CRISPR\/Cas9-Based Genetic Manipulations in Mice. Cells, 9.","DOI":"10.3390\/cells9030546"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"12059","DOI":"10.1038\/s41598-019-48557-8","article-title":"The p21 dependent G2 arrest of the cell cycle in epithelial tubular cells links to the early stage of renal fibrosis","volume":"9","author":"Koyano","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_140","first-page":"1169","article-title":"Increased trabecular bone and improved biomechanics in an osteocalcin null rat model created by CRISPR\/Cas9 technology","volume":"9","author":"Lambert","year":"2016","journal-title":"Dis. Model. Mech."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/crispr.2020.0009","article-title":"Low-Density Lipoprotein Receptor\u2013Related Protein 5\u2013Deficient Rats Have Reduced Bone Mass and Abnormal Development of the Retinal Vasculature","volume":"3","author":"Ubels","year":"2020","journal-title":"CRISPR J."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-35079-y","article-title":"Genetic engineering a large animal model of human hypophosphatasia in sheep","volume":"8","author":"Williams","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"115450","DOI":"10.1016\/j.bone.2020.115450","article-title":"A CRISPR-engineered swine model of COL2A1 deficiency recapitulates altered early skeletal developmental defects in humans","volume":"137","author":"Zhang","year":"2020","journal-title":"Bone"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.theriogenology.2023.05.028","article-title":"Refinements in embryo manipulation applied to CRISPR technology in livestock","volume":"208","author":"Cuadro","year":"2023","journal-title":"Theriogenology"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s12033-021-00347-2","article-title":"Advances and Perspectives in the Application of CRISPR-Cas9 in Livestock","volume":"63","author":"Jabbar","year":"2021","journal-title":"Mol. Biotechnol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.theriogenology.2020.01.063","article-title":"CRISPR in livestock: From editing to printing","volume":"150","author":"Menchaca","year":"2020","journal-title":"Theriogenology"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"292","DOI":"10.21451\/1984-3143-AR2018-0075","article-title":"Directions and applications of CRISPR technology in livestock research","volume":"15","author":"Pericuesta","year":"2018","journal-title":"Anim. Reprod."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/9\/1311\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:39:36Z","timestamp":1760128776000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/9\/1311"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,26]]},"references-count":147,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["biom13091311"],"URL":"https:\/\/doi.org\/10.3390\/biom13091311","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,26]]}}}