{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:21:08Z","timestamp":1792462868012,"version":"4.5.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The modification of the mouse genome by site-specific gene insertion of transgenes and other genetic elements allows the study of gene function in different developmental stages and in the pathogenesis of diseases. Here, we generated a \u201cgenomic safe harbor\u201d Hipp11 (H11) locus-specific knock-in transgenic mouse line in which the albumin promoter is used to drive the expression of the reverse tetracycline transactivator (rtTA) in the liver. The newly generated H11-albumin-rtTA transgenic mice were bred with tetracycline-operator-Histone-2B-green fluorescent protein (TetO-H2BGFP) mice to assess inducibility and tissue-specificity. Expression of the H2BGFP fusion protein was observed exclusively upon doxycycline (Dox) induction in the liver of H11-albumin-rtTA\/TetO-H2BGFP double transgenic mice. To further analyze the ability of the Dox-inducible H11-albumin-rtTA mice to implement conditional DNA recombination, H11-albumin-rtTA transgenic mice were crossed with TetO-Cre and Ai14 mice to generate H11-albumin-rtTA\/TetO-Cre\/Ai14 triple transgenic mice. We successfully confirmed that the Cre-mediated recombination efficiency was as strong in Dox-induced H11-albumin-rtTA \/TetO-Cre\/Ai14 mice as in the control albumin-Cre\/A14 mice. Finally, to characterize the expression-inducing effects of Dox in H11-albumin-rtTA\/TetO-H2BGFP mice in detail, we examined GFP expression in embryos at different developmental stages and found that newly conceived H11-albumin-rtTA\/TetO-H2BGFP embryos of Dox-treated pregnant female mice were expressing reporter GFP by E16.5. Our study demonstrates that these new H11-albumin-rtTA transgenic mice are a powerful and efficient tool for the temporally and spatially conditional manipulation of gene expression in the liver, and illustrates how genetic crosses with these new mice enable the generation of complex multi-locus transgenic animals for mechanistic studies.<\/jats:p>","DOI":"10.1534\/g3.118.200963","type":"journal-article","created":{"date-parts":[[2018,12,27]],"date-time":"2018-12-27T17:55:21Z","timestamp":1545933321000},"page":"591-599","source":"Crossref","is-referenced-by-count":20,"title":["Generation of <i>H11-albumin-rtTA<\/i> Transgenic Mice: A Tool for Inducible Gene Expression in the Liver"],"prefix":"10.1093","volume":"9","author":[{"given":"Yu-Shan","family":"Li","sequence":"first","affiliation":[{"name":"The School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China 453003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran-Ran","family":"Meng","sequence":"additional","affiliation":[{"name":"Transgenic Animal Center, National Institute of Biological Sciences, Beijing, China 102206"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Heze University, Heze, Shandong, China, 274015"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui-Ling","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China 453003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Bin","family":"Li","sequence":"additional","affiliation":[{"name":"The School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China 453003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao-Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Transgenic Animal Center, National Institute of Biological Sciences, Beijing, China 102206"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-Yang","family":"Long","sequence":"additional","affiliation":[{"name":"Transgenic Animal Center, National Institute of Biological Sciences, Beijing, China 102206"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Qi","family":"Li","sequence":"additional","affiliation":[{"name":"Transgenic Animal Center, National Institute of Biological Sciences, Beijing, China 102206"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Transgenic Animal Center, National Institute of Biological Sciences, Beijing, China 102206"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Transgenic Animal Center, National Institute of Biological Sciences, Beijing, China 102206"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,2,1]]},"reference":[{"key":"2021041721124519400_bib1","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/s00294-017-0720-9","article-title":"Improved Tet-On and Tet-Off systems for tetracycline-regulated expression of genes in Candida.","volume":"64","author":"Bijlani","year":"2018","journal-title":"Curr. Genet."},{"key":"2021041721124519400_bib2","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1002\/dvg.20701","article-title":"Generation of a novel rtTA transgenic mouse to induce time-controlled, tissue-specific alterations in Pax2-expressing cells.","volume":"49","author":"Burger","year":"2011","journal-title":"Genesis"},{"key":"2021041721124519400_bib3","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/nature11438","article-title":"The aged niche disrupts muscle stem cell quiescence.","volume":"490","author":"Chakkalakal","year":"2012","journal-title":"Nature"},{"key":"2021041721124519400_bib4","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1053\/j.gastro.2018.05.027","article-title":"Impaired TFEB-Mediated Lysosome Biogenesis and Autophagy Promote Chronic Ethanol-Induced Liver Injury and Steatosis in Mice.","volume":"155","author":"Chao","year":"2018","journal-title":"Gastroenterology"},{"key":"2021041721124519400_bib5","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.plasmid.2010.11.006","article-title":"Construction of a highly-active, liver-specific transcriptional regulatory element through combination of the albumin promoter and alpha-fetoprotein enhancer.","volume":"65","author":"Chen","year":"2011","journal-title":"Plasmid"},{"key":"2021041721124519400_bib6","doi-asserted-by":"publisher","first-page":"6885","DOI":"10.1038\/srep06885","article-title":"Generation of Atoh1-rtTA transgenic mice: a tool for inducible gene expression in hair cells of the inner ear.","volume":"4","author":"Cox","year":"2014","journal-title":"Sci. Rep."},{"key":"2021041721124519400_bib7","doi-asserted-by":"publisher","first-page":"e2403","DOI":"10.1038\/cddis.2016.270","article-title":"Inactivation of Sirt1 in mouse livers protects against endotoxemic liver injury by acetylating and activating NF-kappaB.","volume":"7","author":"Cui","year":"2016","journal-title":"Cell Death Dis."},{"key":"2021041721124519400_bib8","doi-asserted-by":"publisher","first-page":"156","DOI":"10.2174\/1566523216666160524144041","article-title":"Tet-On Systems For Doxycycline-inducible Gene Expression.","volume":"16","author":"Das","year":"2016","journal-title":"Curr. Gene Ther."},{"key":"2021041721124519400_bib9","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.10.008","article-title":"Liver-specific deletion of augmenter of liver regeneration accelerates development of steatohepatitis and hepatocellular carcinoma in mice.","author":"Gandhi","year":"2015"},{"key":"2021041721124519400_bib10","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/j.neuron.2013.03.025","article-title":"Permanent genetic access to transiently active neurons via TRAP: targeted recombination in active populations.","volume":"78","author":"Guenthner","year":"2013","journal-title":"Neuron"},{"key":"2021041721124519400_bib11","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1128\/MCB.21.4.1393-1403.2001","article-title":"Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis.","volume":"21","author":"Hayhurst","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"2021041721124519400_bib12","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1038\/nm.4437","article-title":"Enhancing the precision of genetic lineage tracing using dual recombinases.","volume":"23","author":"He","year":"2017","journal-title":"Nat. Med."},{"key":"2021041721124519400_bib13","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.neuron.2010.09.027","article-title":"Genetic mosaic dissection of Lis1 and Ndel1 in neuronal migration.","volume":"68","author":"Hippenmeyer","year":"2010","journal-title":"Neuron"},{"key":"2021041721124519400_bib14","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1387\/ijdb.15005571","article-title":"Quantitative gene expression profiling reveals a fetal hepatic phenotype of murine ES-derived hepatocytes.","volume":"48","author":"Jochheim","year":"2004","journal-title":"Int. J. Dev. Biol."},{"key":"2021041721124519400_bib15","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/1741-7007-12-25","article-title":"LIM homeodomain transcription factor Isl1 directs normal pyloric development by targeting Gata3.","volume":"12","author":"Li","year":"2014","journal-title":"BMC Biol."},{"key":"2021041721124519400_bib16","doi-asserted-by":"publisher","first-page":"3262","DOI":"10.1111\/febs.14188","article-title":"CRISPR\/Cas9-mediated targeting of the Rosa26 locus produces Cre reporter rat strains for monitoring Cre-loxP-mediated lineage tracing.","volume":"284","author":"Ma","year":"2017","journal-title":"FEBS J."},{"key":"2021041721124519400_bib17","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nn.2467","article-title":"A robust and high-throughput Cre reporting and characterization system for the whole mouse brain.","volume":"13","author":"Madisen","year":"2010","journal-title":"Nat. Neurosci."},{"key":"2021041721124519400_bib18","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1002\/bit.26594","article-title":"RoMo: An efficient strategy for functional mosaic analysis via stochastic Cre recombination and gene targeting in the ROSA26 locus.","volume":"115","author":"Movahedi","year":"2018","journal-title":"Biotechnol. Bioeng."},{"key":"2021041721124519400_bib19","doi-asserted-by":"publisher","first-page":"14253","DOI":"10.1038\/srep14253","article-title":"Highly efficient CRISPR\/Cas9-mediated transgene knockin at the H11 locus in pigs.","volume":"5","author":"Ruan","year":"2015","journal-title":"Sci. Rep."},{"key":"2021041721124519400_bib20","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/nrc3179","article-title":"Safe harbours for the integration of new DNA in the human genome.","volume":"12","author":"Sadelain","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"2021041721124519400_bib21","doi-asserted-by":"publisher","first-page":"e1004299","DOI":"10.1371\/journal.pgen.1004299","article-title":"Rosa26-GFP direct repeat (RaDR-GFP) mice reveal tissue- and age-dependence of homologous recombination in mammals in vivo.","volume":"10","author":"Sukup-Jackson","year":"2014","journal-title":"PLoS Genet."},{"key":"2021041721124519400_bib22","doi-asserted-by":"publisher","first-page":"7902","DOI":"10.1073\/pnas.1019507108","article-title":"Site-specific integrase-mediated transgenesis in mice via pronuclear injection.","volume":"108","author":"Tasic","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021041721124519400_bib23","doi-asserted-by":"publisher","first-page":"e33332","DOI":"10.1371\/journal.pone.0033332","article-title":"Extensions of MADM (mosaic analysis with double markers) in mice.","volume":"7","author":"Tasic","year":"2012","journal-title":"PLoS One"},{"key":"2021041721124519400_bib24","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1002\/dvg.22987","article-title":"Inducible gene modification in the gastric epithelium of Tff1-CreERT2, Tff2-rtTA, Tff3-luc mice.","volume":"54","author":"Thiem","year":"2016","journal-title":"Genesis"},{"key":"2021041721124519400_bib25","author":"Truett","year":"2000"},{"key":"2021041721124519400_bib26","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.neures.2013.11.007","article-title":"A simple and highly efficient method to identify the integration site of a transgene in the animal genome.","volume":"80","author":"Uemura","year":"2014","journal-title":"Neurosci. Res."},{"key":"2021041721124519400_bib27","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nature13589","article-title":"CRISPR-mediated direct mutation of cancer genes in the mouse liver.","volume":"514","author":"Xue","year":"2014","journal-title":"Nature"},{"key":"2021041721124519400_bib28","doi-asserted-by":"publisher","first-page":"7324","DOI":"10.1073\/pnas.96.13.7324","article-title":"Normal growth and development in the absence of hepatic insulin-like growth factor I.","volume":"96","author":"Yakar","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021041721124519400_bib29","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.1038\/nprot.2014.134","article-title":"Generating genetically modified mice using CRISPR\/Cas-mediated genome engineering.","volume":"9","author":"Yang","year":"2014","journal-title":"Nat. Protoc."},{"key":"2021041721124519400_bib30","doi-asserted-by":"publisher","first-page":"3789","DOI":"10.1073\/pnas.94.8.3789","article-title":"Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells.","volume":"94","author":"Zambrowicz","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021041721124519400_bib31","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1038\/sj.gt.3302780","article-title":"Optimization of the Tet-On system for regulated gene expression through viral evolution.","volume":"13","author":"Zhou","year":"2006","journal-title":"Gene Ther."},{"key":"2021041721124519400_bib33","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.3748\/wjg.v18.i16.1892","article-title":"Over-expression of uPA increases risk of liver injury in pAAV-HBV transfected mice.","volume":"18","author":"Zhou","year":"2012","journal-title":"World J Gastroenterol"},{"key":"2021041721124519400_bib32","doi-asserted-by":"publisher","first-page":"e34","DOI":"10.1093\/nar\/gkt1290","article-title":"DICE, an efficient system for iterative genomic editing in human pluripotent stem cells.","volume":"42","author":"Zhu","year":"2014","journal-title":"Nucleic Acids Res."}],"container-title":["G3 Genes|Genomes|Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/g3journal\/article-pdf\/9\/2\/591\/37096685\/g3journal0591.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/g3journal\/article-pdf\/9\/2\/591\/37096685\/g3journal0591.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,17]],"date-time":"2021-04-17T21:12:56Z","timestamp":1618693976000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/g3journal\/article\/9\/2\/591\/6026760"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,1]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2,1]]}},"URL":"https:\/\/doi.org\/10.1534\/g3.118.200963","relation":{},"ISSN":["2160-1836"],"issn-type":[{"value":"2160-1836","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,2,1]]},"published":{"date-parts":[[2019,2,1]]}}}