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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.
AuthorsEleni G Tzortzaki, Dayna Glass, Min Yang, Andrew P Evan, Sharon B Bledsoe, Peter J Stambrook, Amrik Sahota, Jay A Tischfield
JournalThe journal of histochemistry and cytochemistry : official journal of the Histochemistry Society (J Histochem Cytochem) Vol. 50 Issue 12 Pg. 1663-9 (Dec 2002) ISSN: 0022-1554 [Print] United States
PMID12486089 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Kap protein, mouse
  • Proteins
  • RNA, Messenger
  • Adenine Phosphoribosyltransferase
Topics
  • Adenine Phosphoribosyltransferase (deficiency, genetics)
  • Age Factors
  • Animals
  • Female
  • Genotype
  • In Situ Hybridization
  • Kidney (metabolism)
  • Kidney Calculi (metabolism)
  • Male
  • Mice
  • Mice, Knockout
  • Protein Biosynthesis
  • Proteins (genetics)
  • RNA, Messenger (biosynthesis)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sex Factors

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