Claudin-7, -16, and -19 during mouse kidney development

Abstract

Abbreviations: E, embryonic day; P, postnatal; FHHNC, familial hypomagnesaemia with hypercalciuria and nephrocalcinosis; nd, nephric duct; ub, ureteric bud; MET, mesenchymal to epithelial transition.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.

Claudin expression in the rat endolymphatic duct and sac - first insights into regulation of the paracellular barrier by vasopressin

“…The confocal microscopic analysis of the subcellular localization of Claudin 6, 7 and 10 in rat p4 kidney control tissue, revealed similar results as were observed in rat p4 and p31 ED and ES and matched with other Claudin expression studies in the kidney21434647. However, in contrast to the adult ES, none of the former studies visualized Claudin 6 by immunostaining in any nephron segment in rat adult kidney4748.…”

Evolution of the vertebrate claudin gene family: insights from a basal vertebrate, the sea lamprey

“…Cldn 3 transcripts and protein were expressed in the developing mouse metanephric kidney, and overexpression of Cldn3 in in vitro model of kidney tubule formation promoted tubulogenesis (Haddad et al, 2011). Claudin 16 and Claudin 9 expression was observed in mouse embryonic and neonatal kidney (Abuazza et al, 2006, Khairallah et al, 2014. Additionally, Cldn16 knockout mice and humans with mutations in Cldn16 gene exhibit kidney disease (Gupta and Ryan, 2010).…”

“…Cldn 1, 4 and 10 are expressed in the chick mesonephric kidney (Collins et al, 2013). Cldn 7 and 19 are strongly expressed in the developing mouse nephron (Khairallah et al, 2014). Additionally, kidney abnormalities observed in Cldn 2, 4, 7 and 10 knockout mice suggest that these claudins are also important either for embryogenesis or for the adult kidney function (Gupta and Ryan, 2010).…”

Current trends in salivary gland tight junctions

“…Claudin-16 is expressed in several tissues (e.g., in the kidney, 76 mammary glands 77 and enamel) 78 and mutations of this protein cause familial hypomagnesemia, hypercalciuria, and nephrocalcinosis. 79 When claudin-16 is missing, magnesium does not return from the renal tubules to the blood and is lost in the urine, 80 that in turn leads to hypomagnesemia.…”