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Journal of Histochemistry and Cytochemistry, Vol. 50, 1663-1669, December 2002, Copyright © 2002, The Histochemical Society, Inc.


ARTICLE

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

Eleni G. Tzortzakia, Dayna Glassa, Min Yanga, Andrew P. Evanb, Sharon B. Bledsoeb, Peter J. Stambrookc, Amrik Sahotaa, and Jay A. Tischfielda
a Department of Genetics, Rutgers University, Piscataway, New Jersey
b Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana
c Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio

Correspondence to: Amrik Sahota, Dept. of Genetics, Nelson Laboratories, Rutgers University, 604 Allison Road, Piscataway, NJ 08854-8082. E-mail: sahota@nel-exchange.rutgers.edu

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.

(J Histochem Cytochem 50:1663–1669, 2002)

Key Words: adenine phosphoribosyltrans- ferase deficiency, 2,8-dihydroxadenine neph- rolithiasis, kidney androgen-regulated, protein, in situ hybridization, reverse transcription-poly- merase chain reaction in situ, hybridization


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