Reduced aldehyde dehydrogenase activity and arginine vasopressin receptor 2 expression in the kidneys of male TALLYHO/JngJ mice of prediabetic age.

The TALLYHO/JngJ (TH) mouse is a novel polygenic model of type 2 diabetes and exhibits obesity, hyperglycemia (males), hyperinsulinemia, hyperlipidemia, and enlarged pancreatic islets. Since the kidney is damaged by hyperglycemia in other animal models, the present study aimed to determine the kidney phenotype of TH mice using immunoblot and histological analyses of the kidneys of 6-week-old (prediabetic) and 16-week-old TH mice. Interestingly, even 6-week-old male TH mice showed significant increases in kidney weight, compared to C57BL/B6 (B6) mice. Cuboidal parietal epithelium was observed in the Bowman's capsule in male TH mice at the prediabetic age. Water accumulated inside the kidneys of male TH mice in an age-dependent manner, but not in B6 mice. Since Swr/J mice are reported to develop diabetes insipidus and share 86.8% genotype homology with TH mice, the expression level of arginine vasopressin receptor 2 (AVPR2), a candidate protein for diabetes insipidus, was examined and determined to be significantly reduced in the kidneys of prediabetic male TH mice, compared to B6 mice. Aldehyde dehydrogenase (ALDH) activity in the kidneys of prediabetic male TH mice was significantly lower than that in age-matched male B6 mice, while there were no differences between female TH and B6 mice. These results suggest that the kidney phenotype of prediabetic TH mice occurs only in males, accompanied by a reduction in ALDH activity and AVPR2 expression. The kidney phenotype of male TH mice at a prediabetic age becomes evident before the onset of diabetes.