Chloride channels ClC-2 and ICln mRNA expression differs in renal epithelial ontogeny

Chloride channels ClC-2 and ICln mRNA expression differs in renal epithelial ontogeny. Development-dependent mRNA expression of the chloride channels ClC-2 and ICln was studied by quantitative reverse transcriptase-polymerase chain reaction in rat ureteric bud and cortical collecting duct primary monolayer cultures. Abundance of ClC-2 mRNA increased in ureteric bud cells between embryonic day 15 (E15) and E17, peaked at postnatal day 3 (P3), and was down-regulated at P7 when morphogenesis is complete, suggesting a specific embryonic function. Expression of ICln mRNA, in contrast, up-regulated continuously with development

CFTR mRNA and its truncated splice variant (TRN-CFTR) are differentially expressed during collecting duct ontogeny

AbstractThe collecting duct epithelium originates from the embryonic ureter by branching morphogenesis. Ontogeny-dependent changes of CFTR mRNA expression were assessed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in primary monolayer cultures of rat ureteric buds (UB) and cortical collecting ducts, microdissected at different embryonic and postnatal developmental stages. The amount of wild-type CFTR-specific PCR product in UB declined to 20% of the initial value between embryonic gestational day E15 and postnatal day P1. After birth the CFTR product increased transiently between P1 and P7 by a factor of 10 and decreased towards day P14. PCR products specific for TRN-CFTR, a truncated splice variant, however, were low in early embryonic cells, increased markedly between day E17 and P2, and reached a plateau postnatally. Therefore, mRNA encoding TRN-CFTR does not appear to have a specific embryonic-morphogenetic function. By contrast, such function is suggested for wild-type CFTR mRNA as its abundance was high in early embryonic nephrogenesis, as well as during a postnatal period shortly before branching morphogenesis is completed

Novel Allelic Variants in the Canine Cyclooxgenase-2 (Cox-2) Promoter Are Associated with Renal Dysplasia in Dogs

Renal dysplasia (RD) in dogs is a complex disease with a highly variable phenotype and mode of inheritance that does not follow a simple Mendelian pattern. Cox-2 (Cyclooxgenase-2) deficient mice have renal abnormalities and a pathology that has striking similarities to RD in dogs suggesting to us that mutations in the Cox-2 gene could be the cause of RD in dogs. Our data supports this hypothesis. Sequencing of the canine Cox-2 gene was done from clinically affected and normal dogs. Although no changes were detected in the Cox-2 coding region, small insertions and deletions of GC boxes just upstream of the ATG translation start site were found. These sequences are putative SP1 transcription factor binding sites that may represent important cis-acting DNA regulatory elements that govern the expression of Cox-2. A pedigree study of a family of Lhasa apsos revealed an important statistical correlation of these mutant alleles with the disease. We examined an additional 22 clinical cases from various breeds. Regardless of the breed or severity of disease, all of these had one or two copies of the Cox-2 allelic variants. We suggest that the unusual inheritance pattern of RD is due to these alleles, either by changing the pattern of expression of Cox-2 or making Cox-2 levels susceptible to influences of other genes or environmental factors that play an unknown but important role in the development of RD in dogs

Determinants of axial osmotic gradients in the differentiating countercurrent system

The renal medullary countercurrent system differentiates into its final segmental nephron function and geometry during perinatal development. The influence of these changes on the medullary longitudinal osmotic gradient cannot be evaluated by experimental studies. Therefore, a computation analysis using a differential equation model of the renal countercurrent system was applied to quantitate the effect of medullary architecture and solute transport on the concentration profiles for salt and urea in tubules (loop of Henle and collecting duct) and in the central core along the entire medulla during ontogeny. The results indicate that both the changing distribution of loop segments within the medulla and the increase in active salt transport of the individual thick ascending loop determine the magnitude and slope of the axial medullary solute gradients. </jats:p