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

TY - JOUR

T1 - Impaired expression of an organic cation transporter, IMPT1, in a knockout mouse model for kidney stone disease

AU - Tzortzaki, Eleni G.

AU - Yang, Min

AU - Glass, Dayna

AU - Deng, Li

AU - Evan, Andrew P.

AU - Bledsoe, Sharon B.

AU - Stambrook, Peter J.

AU - Sahota, Amrik

AU - Tischfield, Jay A.

N1 - Funding Information: Acknowledgement This work was supported by NIH grants DK38185, ES05652, and ES06096.

PY - 2003/8

Y1 - 2003/8

N2 - 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.

AB - 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.

KW - 2,8-Dihydroxadenine nephrolithiasis

KW - Adenine phosphoribosyltransferase deficiency

KW - Impaired renal transport

KW - Imprinted multimembrane-spanning polyspecific transporter-like gene 1

KW - In situ hybridization

KW - Reverse transcription-polymerase chain reaction

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U2 - 10.1007/s00240-003-0318-1

DO - 10.1007/s00240-003-0318-1

M3 - Article

C2 - 12856169

SN - 0300-5623

VL - 31

SP - 257

EP - 261

JO - Urological Research

JF - Urological Research

IS - 4

ER -