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

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.

• Authors: Eleni G Tzortzaki, Min Yang, Dayna Glass, Li Deng, Andrew P Evan, Sharon B Bledsoe, Peter J Stambrook, Amrik Sahota, Jay A Tischfield
• Journal: Urological research (Urol Res) Vol. 31 Issue 4 Pg. 257-61 (Aug 2003) ISSN: 0300-5623 [Print] Germany
• PMID: 12856169 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

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