Altered mouse cholinephosphotransferase gene expression in kidneys of type 2 diabetic KK/TA mouse.
It is generally considered that genetic factors may contribute to the susceptibility of type 2 diabetic nephropathy. The purpose of the present study is to identify molecules that contribute to the development and/or progression of this disease. Differential display was performed to isolate genes in the kidney using the KK/Ta mouse model of type 2 diabetes. The differential expression of 8 randomly chosen candidate genes (DN1-8) were verified by reverse-transcriptase polymerase chain reaction (RT-PCR) or Northern blot analysis. DN1-3 (Zn-alpha2-glycoprotein, vascular endothelial growth factor receptor [VEGFR]-2, and lactate dehydrogenase [LDH]) were overexpressed and DN7-8 (peroxisome proliferator-activated receptor [PPAR]-interacting protein [PRIP], unknown) were underexpressed in the KK/Ta mouse kidney. DN4-6 (Ezrin, transcobalamin 2, aldo-ketoreductase) did not differ between KK/Ta and control (BALB/c) mice. DN8 only showed no significant sequence similarity to previously reported genes. Molecular cloning revealed that full-length DN8 shares 89% identity with human cholinephosphotransferase 1 (hCHPT1), and we designated it as "putative" mouse cholinephosphotransferase 1 (mCHPT1). The putative mCHPT1 gene was most closely mapped to the D10Mit94 locus with the highest logarithm of odds (lod) score. In situ hybridization revealed the levels of glomerular putative mCHPT1 in BALB/c mice tended to be slightly higher than those in KK/Ta mice. The altered renal mRNA expression of these genes may be involved in the development and/or progression of diabetic nephropathy.
Gohda
Tomohito
T
Division of Nephrology, Department of Internal Medicine, Jutendo University School of Medicine, Tokyo, Japan.
Tanimoto
Mitsuo
M
Shiina
Kenji
K
Ito
Takamichi
T
Kobayashi
Michimasa
M
Hagiwara
Shinji
S
Kaneko
Shigeru
S
Makita
Yuichiro
Y
Funabiki
Kazuhiko
K
Horikoshi
Satoshi
S
Tomino
Yasuhiko
Y
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000235:genetics*; D002798:Diacylglycerol Cholinephosphotransferase / Q000096:biosynthesis* / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D017403:In Situ Hybridization; D007668:Kidney / Q000201:enzymology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018076:DNA, Complementary; D012333:RNA, Messenger; D002798:Diacylglycerol Cholinephosphotransferase