{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:59:54Z","timestamp":1790438394906,"version":"4.1.0"},"reference-count":83,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","funder":[{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","award":["NIDDK DK90728"],"award-info":[{"award-number":["NIDDK DK90728"]}],"id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007048","name":"Mayo Foundation for Medical Education and Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007048","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mayo Clinic Center for Biomedical Discovery"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>\n                      Zebrafish embryos are well recognized for their value in studying polycystic kidney disease, but they cannot fully recapitulate the pathogenesis of the disease. The establishment of\n                      <jats:italic toggle=\"yes\">tmem67<\/jats:italic>\n                      <jats:sup>e3\/e3<\/jats:sup>\n                      mutants provides the first adult zebrafish model for cystogenesis. The model exhibits progressive renal cysts and enables the discernment of compensational effects from pathogenic events. Development of a tissue-clearing, whole-mount imaging protocol allows the analysis of renal cysts and cilia abnormality at a single-nephron resolution. Evidence also indicates potential benefit of mammalian target of rapamycin inhibition in\n                      <jats:italic toggle=\"yes\">tmem67<\/jats:italic>\n                      -based cystogenesis. Combining powerful genetics and phenotyping tools, this novel adult zebrafish model shall facilitate mechanistic studies and therapeutic development for cystic diseases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although zebrafish embryos have been used to study ciliogenesis and model polycystic kidney disease (PKD), adult zebrafish remain unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Transcription activator-like effector nucleases (TALEN) technology was used to generate mutant for\u00a0\n                      <jats:italic toggle=\"yes\">tmem67<\/jats:italic>\n                      , the homolog of the mammalian causative gene for Meckel syndrome type 3 (MKS3). Classic 2D and optical-clearing 3D imaging of an isolated adult zebrafish kidney were used to examine cystic and ciliary phenotypes. A hypomorphic\n                      <jats:italic toggle=\"yes\">mtor<\/jats:italic>\n                      strain or rapamycin was used to inhibit mTOR activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Adult\n                      <jats:italic toggle=\"yes\">tmem67<\/jats:italic>\n                      zebrafish developed progressive mesonephric cysts that share conserved features of mammalian cystogenesis, including a switch of cyst origin with age and an increase in proliferation of cyst-lining epithelial cells. The mutants had shorter and fewer distal single cilia and greater numbers of multiciliated cells (MCCs). Absence of a single cilium preceded cystogenesis, and expansion of MCCs occurred after pronephric cyst formation and was inversely correlated with the severity of renal cysts in young adult zebrafish, suggesting a primary defect and an adaptive action, respectively. Finally, the mutants exhibited hyperactive mTOR signaling. mTOR inhibition ameliorated renal cysts in both the embryonic and adult zebrafish models; however, it only rescued ciliary abnormalities in the adult mutants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Adult zebrafish\n                      <jats:italic toggle=\"yes\">tmem67<\/jats:italic>\n                      mutants offer a new vertebrate model for renal cystic diseases, in which cilia morphology can be analyzed at a single-nephron resolution and mTOR inhibition proves to be a candidate therapeutic strategy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2020070991","type":"journal-article","created":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T16:01:20Z","timestamp":1613059280000},"page":"822-836","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":19,"title":["mtor Haploinsufficiency Ameliorates Renal Cysts and Cilia Abnormality in Adult Zebrafish tmem67 Mutants"],"prefix":"10.1681","volume":"32","author":[{"given":"Ping","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5304-6593","authenticated-orcid":false,"given":"Peter C.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota"},{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota"},{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,2,11]]},"reference":[{"key":"B1-20240826","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/ng1713","article-title":"The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat","volume":"38","author":"Smith","year":"2006","journal-title":"Nat Genet"},{"key":"B2-20240826","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s00439-007-0341-3","article-title":"Molecular diagnostics of Meckel-Gruber syndrome highlights phenotypic differences between MKS1 and MKS3","volume":"121","author":"Consugar","year":"2007","journal-title":"Hum Genet"},{"key":"B3-20240826","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1002\/humu.9489","article-title":"Spectrum of MKS1 and MKS3 mutations in Meckel syndrome: A genotype-phenotype correlation. Mutation in brief #960. Online","volume":"28","author":"Khaddour","year":"2007","journal-title":"Hum Mutat"},{"key":"B4-20240826","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1086\/510499","article-title":"The Meckel-Gruber syndrome gene, MKS3, is mutated in Joubert syndrome","volume":"80","author":"Baala","year":"2007","journal-title":"Am J Hum Genet"},{"key":"B5-20240826","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1002\/ajmg.a.33727","article-title":"Craniofacial ciliopathies: A new classification for craniofacial disorders","volume":"152A","author":"Brugmann","year":"2010","journal-title":"Am J Med Genet A"},{"key":"B6-20240826","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3233\/PGE-14090","article-title":"Unraveling the genetics of Joubert and Meckel-Gruber syndromes","volume":"3","author":"Szymanska","year":"2014","journal-title":"J Pediatr Genet"},{"key":"B7-20240826","first-page":"2102","article-title":"Meckel gruber syndrome","volume":"7","author":"Roy","year":"2013","journal-title":"J Clin Diagn Res"},{"key":"B8-20240826","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1002\/ar.a.20022","article-title":"Development of multiorgan pathology in the wpk rat model of polycystic kidney disease","volume":"277","author":"Gattone","year":"2004","journal-title":"Anat Rec A Discov Mol Cell Evol Biol"},{"key":"B9-20240826","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1681\/ASN.2008040412","article-title":"A mouse model for Meckel syndrome type 3","volume":"20","author":"Cook","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"B10-20240826","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1038\/s41598-017-01519-4","article-title":"An ovine hepatorenal fibrocystic model of a Meckel-like syndrome associated with dysmorphic primary cilia and TMEM67 mutations","volume":"7","author":"Stayner","year":"2017","journal-title":"Sci Rep"},{"key":"B11-20240826","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1093\/hmg\/ddp272","article-title":"Ciliary and centrosomal defects associated with mutation and depletion of the Meckel syndrome genes MKS1 and MKS3","volume":"18","author":"Tammachote","year":"2009","journal-title":"Hum Mol Genet"},{"key":"B12-20240826","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1093\/hmg\/ddt054","article-title":"The Meckel syndrome protein meckelin (TMEM67) is a key regulator of cilia function but is not required for tissue planar polarity","volume":"22","author":"Leightner","year":"2013","journal-title":"Hum Mol Genet"},{"key":"B13-20240826","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/ng.891","article-title":"A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition","volume":"43","author":"Garcia-Gonzalo","year":"2011","journal-title":"Nat Genet"},{"key":"B14-20240826","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1093\/hmg\/dds546","article-title":"Variable expressivity of ciliopathy neurological phenotypes that encompass Meckel-Gruber syndrome and Joubert syndrome is caused by complex de-regulated ciliogenesis, Shh and Wnt signalling defects","volume":"22","author":"Abdelhamed","year":"2013","journal-title":"Hum Mol Genet"},{"key":"B15-20240826","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1242\/dmm.019083","article-title":"The Meckel-Gruber syndrome protein TMEM67 controls basal body positioning and epithelial branching morphogenesis in mice via the non-canonical Wnt pathway","volume":"8","author":"Abdelhamed","year":"2015","journal-title":"Dis Model Mech"},{"key":"B16-20240826","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1083\/jcb.201111146","article-title":"Scoring a backstage pass: Mechanisms of ciliogenesis and ciliary access","volume":"197","author":"Garcia-Gonzalo","year":"2012","journal-title":"J Cell Biol"},{"key":"B17-20240826","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1093\/hmg\/ddl459","article-title":"The Meckel-Gruber Syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation","volume":"16","author":"Dawe","year":"2007","journal-title":"Hum Mol Genet"},{"key":"B18-20240826","doi-asserted-by":"crossref","first-page":"4655","DOI":"10.1242\/dev.125.23.4655","article-title":"Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function","volume":"125","author":"Drummond","year":"1998","journal-title":"Development"},{"key":"B19-20240826","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.1242\/dev.01240","article-title":"A genetic screen in zebrafish identifies cilia genes as a principal cause of cystic kidney","volume":"131","author":"Sun","year":"2004","journal-title":"Development"},{"key":"B20-20240826","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1242\/dev.02827","article-title":"Zebrafish curly up encodes a Pkd2 ortholog that restricts left-side-specific expression of southpaw","volume":"134","author":"Schottenfeld","year":"2007","journal-title":"Development"},{"key":"B21-20240826","first-page":"158","article-title":"Autophagy activators suppress cystogenesis in an autosomal dominant polycystic kidney disease model","volume":"26","author":"Zhu","year":"2017","journal-title":"Hum Mol Genet"},{"key":"B22-20240826","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/bs.mcb.2016.04.016","article-title":"Analysis of cilia structure and function in zebrafish","volume":"133","author":"Leventea","year":"2016","journal-title":"Methods Cell Biol"},{"key":"B23-20240826","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1242\/dev.01772","article-title":"Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer\u2019s vesicle is required for normal organogenesis","volume":"132","author":"Kramer-Zucker","year":"2005","journal-title":"Development"},{"key":"B24-20240826","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1371\/journal.pgen.0030189","article-title":"The cdx genes and retinoic acid control the positioning and segmentation of the zebrafish pronephros","volume":"3","author":"Wingert","year":"2007","journal-title":"PLoS Genet"},{"key":"B25-20240826","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1242\/dev.02806","article-title":"Notch signaling controls the differentiation of transporting epithelia and multiciliated cells in the zebrafish pronephros","volume":"134","author":"Liu","year":"2007","journal-title":"Development"},{"key":"B26-20240826","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1371\/journal.pgen.0030018","article-title":"Jagged2a-notch signaling mediates cell fate choice in the zebrafish pronephric duct","volume":"3","author":"Ma","year":"2007","journal-title":"PLoS Genet"},{"key":"B27-20240826","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.trsl.2013.10.003","article-title":"New tides: Using zebrafish to study renal regeneration","volume":"163","author":"McCampbell","year":"2014","journal-title":"Transl Res"},{"issue":"90","key":"B28-20240826","first-page":"e51644","article-title":"Analysis of nephron composition and function in the adult zebrafish kidney","author":"McCampbell","year":"2014","journal-title":"J Vis Exp"},{"key":"B29-20240826","doi-asserted-by":"crossref","first-page":"547636","DOI":"10.1155\/2015\/547636","article-title":"Atlas of cellular dynamics during zebrafish adult kidney regeneration","volume":"2015","author":"McCampbell","year":"2015","journal-title":"Stem Cells Int"},{"key":"B30-20240826","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/dvg.22846","article-title":"Development of the zebrafish mesonephros","volume":"53","author":"Diep","year":"2015","journal-title":"Genesis"},{"key":"B31-20240826","doi-asserted-by":"crossref","first-page":"e121396","DOI":"10.1172\/jci.insight.121396","article-title":"Multiscale light-sheet for rapid imaging of cardiopulmonary system","volume":"3","author":"Ding","year":"2018","journal-title":"JCI Insight"},{"key":"B32-20240826","doi-asserted-by":"crossref","first-page":"e48183","DOI":"10.7554\/eLife.48183","article-title":"Spatiotemporal dynamics and heterogeneity of renal lymphatics in mammalian development and cystic kidney disease","volume":"8","author":"Jafree","year":"2019","journal-title":"eLife"},{"issue":"149","key":"B33-20240826","first-page":"e60002","article-title":"Optical clearing and imaging of immunolabeled kidney tissue","author":"Saritas","year":"2019","journal-title":"J Vis Exp"},{"key":"B34-20240826","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1161\/CIRCRESAHA.111.248260","article-title":"Haploinsufficiency of target of rapamycin attenuates cardiomyopathies in adult zebrafish","volume":"109","author":"Ding","year":"2011","journal-title":"Circ Res"},{"key":"B35-20240826","doi-asserted-by":"crossref","first-page":"e82","DOI":"10.1093\/nar\/gkr218","article-title":"Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting","volume":"39","author":"Cermak","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"B36-20240826","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/nbt.1939","article-title":"Heritable gene targeting in zebrafish using customized TALENs","volume":"29","author":"Huang","year":"2011","journal-title":"Nat Biotechnol"},{"key":"B37-20240826","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nbt.1755","article-title":"A TALE nuclease architecture for efficient genome editing","volume":"29","author":"Miller","year":"2011","journal-title":"Nat Biotechnol"},{"key":"B38-20240826","doi-asserted-by":"crossref","first-page":"E813","DOI":"10.1002\/humu.21057","article-title":"Mutation spectrum of Meckel syndrome genes: One group of syndromes or several distinct groups?","volume":"30","author":"Tallila","year":"2009","journal-title":"Hum Mutat"},{"key":"B39-20240826","first-page":"E1319","article-title":"Novel TMEM67 mutations and genotype-phenotype correlates in meckelin-related ciliopathies","volume":"31","author":"Iannicelli","year":"2010","journal-title":"Hum Mutat"},{"key":"B40-20240826","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.ydbio.2006.11.034","article-title":"Depletion of Med10 enhances Wnt and suppresses Nodal signaling during zebrafish embryogenesis","volume":"303","author":"Lin","year":"2007","journal-title":"Dev Biol"},{"key":"B41-20240826","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1242\/dev.071746","article-title":"Wnt\/\u03b2-catenin signaling directly regulates Foxj1 expression and ciliogenesis in zebrafish Kupffer\u2019s vesicle","volume":"139","author":"Caron","year":"2012","journal-title":"Development"},{"key":"B42-20240826","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1242\/bio.012088","article-title":"Both ciliary and non-ciliary functions of Foxj1a confer Wnt\/\u03b2-catenin signaling in zebrafish left-right patterning","volume":"4","author":"Zhu","year":"2015","journal-title":"Biol Open"},{"key":"B43-20240826","doi-asserted-by":"crossref","first-page":"4257","DOI":"10.1172\/JCI64313","article-title":"Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity","volume":"122","author":"Hopp","year":"2012","journal-title":"J Clin Invest"},{"key":"B44-20240826","first-page":"811","article-title":"Long-term drug administration in the adult zebrafish using oral gavage for cancer preclinical studies","volume":"9","author":"Dang","year":"2016","journal-title":"Dis Model Mech"},{"key":"B45-20240826","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/ki.2009.128","article-title":"Autosomal dominant polycystic kidney disease: The last 3 years","volume":"76","author":"Torres","year":"2009","journal-title":"Kidney Int"},{"key":"B46-20240826","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1172\/JCI72272","article-title":"Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease","volume":"124","author":"Harris","year":"2014","journal-title":"J Clin Invest"},{"key":"B47-20240826","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1523-1755.2005.00378.x","article-title":"Fish mesonephric model of polycystic kidney disease in medaka (Oryzias latipes) pc mutant","volume":"68","author":"Mochizuki","year":"2005","journal-title":"Kidney Int"},{"key":"B48-20240826","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41572-018-0047-y","article-title":"Polycystic kidney disease","volume":"4","author":"Bergmann","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"B49-20240826","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1093\/ndt\/gfi181","article-title":"Inhibition of mTOR with sirolimus slows disease progression in Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD)","volume":"21","author":"Wahl","year":"2006","journal-title":"Nephrol Dial Transplant"},{"key":"B50-20240826","doi-asserted-by":"crossref","first-page":"5466","DOI":"10.1073\/pnas.0509694103","article-title":"The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease","volume":"103","author":"Shillingford","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B51-20240826","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1681\/ASN.2009040421","article-title":"Rapamycin ameliorates PKD resulting from conditional inactivation of Pkd1","volume":"21","author":"Shillingford","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"B52-20240826","doi-asserted-by":"crossref","first-page":"e6299","DOI":"10.1371\/journal.pone.0006299","article-title":"Polycystic kidney disease in the medaka (Oryzias latipes) pc mutant caused by a mutation in the Gli-Similar3 (glis3) gene","volume":"4","author":"Hashimoto","year":"2009","journal-title":"PLoS One"},{"key":"B53-20240826","doi-asserted-by":"crossref","first-page":"F1040","DOI":"10.1152\/ajprenal.00394.2010","article-title":"Characterization of mesonephric development and regeneration using transgenic zebrafish","volume":"299","author":"Zhou","year":"2010","journal-title":"Am J Physiol Renal Physiol"},{"key":"B54-20240826","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nature09669","article-title":"Identification of adult nephron progenitors capable of kidney regeneration in zebrafish","volume":"470","author":"Diep","year":"2011","journal-title":"Nature"},{"issue":"102","key":"B55-20240826","first-page":"e51912","article-title":"Kidney regeneration in adult zebrafish by gentamicin induced injury","author":"Kamei","year":"2015","journal-title":"J Vis Exp"},{"key":"B56-20240826","doi-asserted-by":"crossref","first-page":"dev168294","DOI":"10.1242\/dev.168294","article-title":"Wnt signaling mediates new nephron formation during zebrafish kidney regeneration","volume":"146","author":"Kamei","year":"2019","journal-title":"Development"},{"key":"B57-20240826","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ydbio.2019.06.011","article-title":"Fibroblast growth factor signaling mediates progenitor cell aggregation and nephron regeneration in the adult zebrafish kidney","volume":"454","author":"Gallegos","year":"2019","journal-title":"Dev Biol"},{"key":"B58-20240826","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1093\/hmg\/ddn045","article-title":"Acute kidney injury and aberrant planar cell polarity induce cyst formation in mice lacking renal cilia","volume":"17","author":"Patel","year":"2008","journal-title":"Hum Mol Genet"},{"key":"B59-20240826","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/nm.2010","article-title":"Impaired Wnt-beta-catenin signaling disrupts adult renal homeostasis and leads to cystic kidney ciliopathy","volume":"15","author":"Lancaster","year":"2009","journal-title":"Nat Med"},{"key":"B60-20240826","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/nature14580","article-title":"Genetic compensation induced by deleterious mutations but not gene knockdowns","volume":"524","author":"Rossi","year":"2015","journal-title":"Nature"},{"key":"B61-20240826","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/s41586-019-1064-z","article-title":"Genetic compensation triggered by mutant mRNA degradation","volume":"568","author":"El-Brolosy","year":"2019","journal-title":"Nature"},{"key":"B62-20240826","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/s41586-019-1057-y","article-title":"PTC-bearing mRNA elicits a genetic compensation response via Upf3a and COMPASS components","volume":"568","author":"Ma","year":"2019","journal-title":"Nature"},{"key":"B63-20240826","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1167\/iovs.16-20326","article-title":"The ciliopathy gene ahi1 is required for zebrafish cone photoreceptor outer segment morphogenesis and survival","volume":"58","author":"Lessieur","year":"2017","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B64-20240826","first-page":"227","article-title":"[Cilia in the fetal kidney of man]","volume":"143","author":"Zimmermann","year":"1971","journal-title":"Beitr Pathol"},{"key":"B65-20240826","first-page":"609","article-title":"Ciliated human renal proximal tubular cells. Observations in three cases of hypercalcemia","volume":"53","author":"Duffy","year":"1968","journal-title":"Am J Pathol"},{"key":"B66-20240826","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3109\/01913129509064222","article-title":"Ciliated renal tubular cells in crescentic glomerulonephritis","volume":"19","author":"Hassan","year":"1995","journal-title":"Ultrastruct Pathol"},{"key":"B67-20240826","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3109\/01913128409018587","article-title":"Cilia in the human kidney","volume":"6","author":"Katz","year":"1984","journal-title":"Ultrastruct Pathol"},{"key":"B68-20240826","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1053\/j.ajkd.2005.02.019","article-title":"Detection of proximal tubular motile cilia in a patient with renal sarcoidosis associated with hypercalcemia","volume":"45","author":"Ong","year":"2005","journal-title":"Am J Kidney Dis"},{"key":"B69-20240826","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/sj.ki.5002294","article-title":"A mouse model of autosomal recessive polycystic kidney disease with biliary duct and proximal tubule dilatation","volume":"72","author":"Woollard","year":"2007","journal-title":"Kidney Int"},{"key":"B70-20240826","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nrm.2017.21","article-title":"The development and functions of multiciliated epithelia","volume":"18","author":"Spassky","year":"2017","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B71-20240826","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/nrm952","article-title":"Intraflagellar transport","volume":"3","author":"Rosenbaum","year":"2002","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B72-20240826","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/nature07753","article-title":"FGF signalling during embryo development regulates cilia length in diverse epithelia","volume":"458","author":"Neugebauer","year":"2009","journal-title":"Nature"},{"key":"B73-20240826","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nrm3085","article-title":"Ciliogenesis: Building the cell\u2019s antenna","volume":"12","author":"Ishikawa","year":"2011","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B74-20240826","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1242\/dev.074666","article-title":"Switching on cilia: Transcriptional networks regulating ciliogenesis","volume":"141","author":"Choksi","year":"2014","journal-title":"Development"},{"key":"B75-20240826","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1681\/ASN.2008101105","article-title":"Renal primary cilia lengthen after acute tubular necrosis","volume":"20","author":"Verghese","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"B76-20240826","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.cub.2009.11.072","article-title":"Identification of signaling pathways regulating primary cilium length and flow-mediated adaptation","volume":"20","author":"Besschetnova","year":"2010","journal-title":"Curr Biol"},{"key":"B77-20240826","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1093\/hmg\/ddn325","article-title":"The tuberous sclerosis proteins regulate formation of the primary cilium via a rapamycin-insensitive and polycystin 1-independent pathway","volume":"18","author":"Hartman","year":"2009","journal-title":"Hum Mol Genet"},{"key":"B78-20240826","doi-asserted-by":"crossref","first-page":"F584","DOI":"10.1152\/ajprenal.00141.2012","article-title":"Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules","volume":"303","author":"Armour","year":"2012","journal-title":"Am J Physiol Renal Physiol"},{"key":"B79-20240826","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1093\/hmg\/ddn384","article-title":"Zebrafish Tsc1 reveals functional interactions between the cilium and the TOR pathway","volume":"18","author":"DiBella","year":"2009","journal-title":"Hum Mol Genet"},{"key":"B80-20240826","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1093\/hmg\/ddp149","article-title":"Defects in cell polarity underlie TSC and ADPKD-associated cystogenesis","volume":"18","author":"Bonnet","year":"2009","journal-title":"Hum Mol Genet"},{"key":"B81-20240826","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1007\/s00018-018-2761-8","article-title":"TSC1 and TSC2 regulate cilia length and canonical Hedgehog signaling via different mechanisms","volume":"75","author":"Rosengren","year":"2018","journal-title":"Cell Mol Life Sci"},{"key":"B82-20240826","first-page":"91","article-title":"Rapamycin increases length and mechanosensory function of primary cilia in renal epithelial and vascular endothelial cells","volume":"2","author":"Sherpa","year":"2016","journal-title":"Int Educ Res J"},{"key":"B83-20240826","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1073\/pnas.1112834109","article-title":"Target-of-rapamycin complex 1 (Torc1) signaling modulates cilia size and function through protein synthesis regulation","volume":"109","author":"Yuan","year":"2012","journal-title":"Proc Natl Acad Sci U S A"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.2020070991","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:24:38Z","timestamp":1786130678000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.2020070991"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,11]]},"references-count":83,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2020070991","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2019.12.20.883710","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.3410\/f.739542850.793587323","asserted-by":"object"}]},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,11]]},"assertion":[{"value":"2020-07-14","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-21","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}