title: Claudin-7, -16, and -19 during mouse kidney development.
abstract: Members of the claudin family of tight junction proteins are critical for establishing epithelial barriers and for the regulation of paracellular transport. To understand their roles during kidney development, we first performed RT-PCR analyses and determined that 23 claudin family members were expressed in embryonic day (E) 13.5 mouse kidneys. Based on their developmental expression and phenotypes in mouse models, we hypothesized that 3 claudin members could affect nephron formation during kidney development. Using whole mount in situ hybridization and immunohistochemistry, we demonstrated that Claudin-7 (Cldn7) was expressed in the nephric duct, the emerging ureteric bud, and in tubules derived from ureteric bud branching morphogenesis. In contrast, Claudin-16 (Cldn16) and Claudin-19 (Cldn19) were expressed at later stages of kidney development in immature renal tubules that become the Loop of Henle. To determine if a loss of these claudins would perturb kidney development, we examined newborn kidneys from mutant mouse models lacking Cldn7 or Cldn16. In both models, we noted no evidence for any congenital renal malformation and quantification of nephron number did not reveal a decrease in nephron number when compared to wildtype littermates. In summary, Cldn7, Cldn16, and Cldn19 are expressed in different epithelial lineages during kidney development. Mice lacking Cldn7 or Cldn16 do not have defects in de novo nephron formation, and this suggests that these claudins primarily function to regulate paracellular transport in the mature nephron.
authors.affiliation: Department of Human Genetics; McGill University ; Montreal, Quebec, Canada.
authors.forename: Halim
authors.initials: H
authors.lastname: Khairallah
authors.affiliation: The Research Institute of the McGill University Health Center; Montreal Children's Hospital ; Montreal, Quebec, Canada.
authors.forename: Jasmine
authors.initials: J
authors.lastname: El Andalousi
authors.affiliation: The Research Institute of the McGill University Health Center; Montreal Children's Hospital ; Montreal, Quebec, Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: Simard
authors.affiliation: Department of Human Genetics; McGill University ; Montreal, Quebec, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Haddad
authors.affiliation: Department of Anatomy and Cell Biology; Brody School of Medicine at East Carolina University ; Greenville, NC USA.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Washington University Renal Division ; St. Louis, MO USA.
authors.forename: Jianghui
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Human Genetics; McGill University ; Montreal, Quebec, Canada ; The Research Institute of the McGill University Health Center; Montreal Children's Hospital ; Montreal, Quebec, Canada ; Department of Pediatrics; McGill University ; Montreal, Quebec, Canada.
authors.forename: Aimee K
authors.initials: AK
authors.lastname: Ryan
authors.affiliation: Department of Human Genetics; McGill University ; Montreal, Quebec, Canada ; The Research Institute of the McGill University Health Center; Montreal Children's Hospital ; Montreal, Quebec, Canada ; Department of Pediatrics; McGill University ; Montreal, Quebec, Canada.
authors.forename: Indra R
authors.initials: IR
authors.lastname: Gupta
keywords: E, embryonic day; FHHNC, familial hypomagnesaemia with hypercalciuria and nephrocalcinosis; Loop of Henle; MET, mesenchymal to epithelial transition; P, postnatal; nd, nephric duct; nephrogenesis; renal branching morphogenesis; tubule differentiation; ub, ureteric bud