title: 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.affiliation: Department of Genetics, Rutgers University, 604 Allison Road, NJ 08854-8082, Piscataway, USA.
authors.forename: Eleni G
authors.initials: EG
authors.lastname: Tzortzaki
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Dayna
authors.initials: D
authors.lastname: Glass
authors.forename: Li
authors.initials: L
authors.lastname: Deng
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Evan
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Bledsoe
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Stambrook
authors.forename: Amrik
authors.initials: A
authors.lastname: Sahota
authors.forename: Jay A
authors.initials: JA
authors.lastname: Tischfield
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives*; D000228:Adenine Phosphoribosyltransferase / Q000172:deficiency / Q000235:genetics; D000818:Animals; D001692:Biological Transport; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D018392:Genomic Imprinting; D007669:Kidney Calculi / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D027701:Organic Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D027701:Organic Cation Transport Proteins; C111653:SLC22A18 protein, human; C002993:2,8-dihydroxyadenine; D000228:Adenine Phosphoribosyltransferase; D000225:Adenine