Gender- and Age-dependent Changes in Kidney Androgen Protein mRNA Expression in a Knockout Mouse Model for Nephrolithiasis

Abstract

Kidney androgen-regulated protein (Kap) is the most abundant protein in the mouse kidney, but its function is unknown. We previously observed a significant decrease in Kap mRNA expression in whole kidney tissue from male mice with adenine phosphoribosyltransferase (APRT) deficiency and 2,8-dihydroxyadenine (DHA) nephrolithiasis. The disease phenotype is more severe in male mice and is age-dependent. To identify the cellular basis for differential Kap expression, we used in situ hybridization (ISH) and reverse transcription-polymerase chain reaction ISH (RT-PCR ISH) to identify the cell types expressing this mRNA in paraffin-embedded kidney sections. In 1-month-old wild-type male mice, Kap was detected primarily in S3 proximal tubule segments, but expression was very low in female mice. In 1-month-old APRT-deficient male mice, Kap expression was decreased significantly and was undetectable in female mice. Kap mRNA was not detected in 3- or 6-month-old mice using our standard ISH protocol, but we observed intense cytoplasmic staining in S3 proximal tubules in wild-type male mice of these age groups using an improved RT-PCR ISH procedure. Our studies demonstrate age-, gender-, and APRT genotype-dependent changes in Kap mRNA expression in mouse kidney. Kap expression is under multihormonal control, and hormonal changes in DHA-induced nephrolithiasis may account for the decreased Kap expression in APRT-deficient mice.