title: Col2-Cre recombinase is co-expressed with endogenous type II collagen in embryonic renal epithelium and drives development of polycystic kidney disease following inactivation of ciliary genes.
abstract: Here we report on the severe defects in renal epithelium induced by the transgenic Col2-Cre line used previously for skeletal tissue-specific gene targeting. We demonstrate that conditional ablation of the Kif3a or Pkd1 genes encoding primary cilium/intraflagellar transport-associated proteins using type II collagen-specific Cre transgenic strain results in a severe form of polycystic kidney disease in mice. We detect Col2-Cre recombinase expression in kidney epithelium, which reflects expression of the endogenous Col1alpha(II) gene in the embryonic renal tubules. We determine the exon 2-containing splice variant of the Col1alpha(II) gene as a major transcript expressed in kidney. Furthermore, the confocal immunocytochemical analysis demonstrates deposition of the type II collagen within the mesenchymal-epithelial renal tissue interfaces and its co-localization with the basement membrane marker collagen IV during embryonic kidney morphogenesis.
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA. elona_kolpakova@hms.harvard.edu
authors.forename: Elona
authors.initials: E
authors.lastname: Kolpakova-Hart
authors.forename: Claudia
authors.initials: C
authors.lastname: Nicolae
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Bjorn R
authors.initials: BR
authors.lastname: Olsen
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism*; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000033:anatomy & histology* / Q000378:metabolism / Q000473:pathology; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D050396:TRPP Cation Channels / Q000378:metabolism
chemical_list: D024043:Collagen Type II; D019426:Integrases; D016547:Kinesins; D020033:Protein Isoforms; D050396:TRPP Cation Channels; C490202:Kif3a protein, mouse; C074152:kinesin-II; C045073:Cre recombinase