Impaired expression of an organic cation transporter, IMPT1, in a knockout mouse model for kidney stone disease

Urol Res. 2003 Aug;31(4):257-61. doi: 10.1007/s00240-003-0318-1. Epub 2003 Jul 11.

Abstract

The imprinted multimembrane-spanning polyspecific transporter-like gene 1 ( IMPT1) encodes a predicted protein with organic cation transport capabilities. As a first step in understanding the function of IMPT1, we identified the renal structures expressing this gene in knockout mice with adenine phosphoribosyltransferase (APRT) deficiency and 2,8-dihydroxyadenine (DHA) nephrolithiasis. IMPT1 mRNA was not detected using a standard in situ hybridization (ISH) protocol, but we observed intense staining in cortico-medullary tubules and glomeruli in wild-type mice using an improved reverse transcription-polymerase chain reaction (RT-PCR) ISH procedure. IMPT1 mRNA expression was significantly decreased in the cortical region in kidney sections from APRT-deficient male mice. APRT-deficient female mice are less severely affected by DHA-induced kidney stone disease, and we observed only a modest reduction in IMPT1 expression in kidneys from these mice. IMPT1 expression in APRT heterozygous mice was comparable to that in wild-type mice, suggesting imprinting of one of the parental alleles. These findings suggest that decreased IMPT1 mRNA expression may contribute to the impaired renal function in APRT-deficient male mice, and that RT-PCR ISH is a valuable tool for localizing the site of expression of transcripts that are not detectable using standard ISH procedures.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine Phosphoribosyltransferase / deficiency
  • Adenine Phosphoribosyltransferase / genetics
  • Animals
  • Biological Transport
  • Female
  • Gene Dosage
  • Gene Expression
  • Genomic Imprinting
  • Kidney Calculi / chemically induced
  • Kidney Calculi / metabolism*
  • Kidney Calculi / physiopathology*
  • Male
  • Mice
  • Mice, Knockout
  • Organic Cation Transport Proteins / genetics*
  • Organic Cation Transport Proteins / metabolism*

Substances

  • Organic Cation Transport Proteins
  • SLC22A18 protein, human
  • 2,8-dihydroxyadenine
  • Adenine Phosphoribosyltransferase
  • Adenine