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非胰岛素依赖型糖尿病大鼠模型“OLETF”的遗传剖析:(OLETF×BN)×OLETF的数量性状基因座分析

Genetic dissection of "OLETF," a rat model for non-insulin-dependent diabetes mellitus: quantitative trait locus analysis of (OLETF x BN) x OLETF.

作者信息

Watanabe T K, Okuno S, Oga K, Mizoguchi-Miyakita A, Tsuji A, Yamasaki Y, Hishigaki H, Kanemoto N, Takagi T, Takahashi E, Irie Y, Nakamura Y, Tanigami A

机构信息

Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima, 771-0192, Japan.

出版信息

Genomics. 1999 Jun 15;58(3):233-9. doi: 10.1006/geno.1999.5789.

DOI:10.1006/geno.1999.5789
PMID:10373320
Abstract

To identify genetic determinants relevant to non-insulin-dependent diabetes mellitus (NIDDM), we performed a genome-wide analysis for quantitative trait loci (QTLs) using 359 backcross progeny of the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The OLETF strain is a well-studied animal model of obese NIDDM, with features of hyperinsulinemia, hyperglycemia, insulin resistance, and abundant abdominal fat. Our extensive genomic scanning with 218 markers revealed nine significant QTLs, including a strong determinant of obesity on chromosome 1 (Dmo1: LOD = 13.99, for body weight). Two highly significant QTLs for glucose homeostasis were found, one on chromosome 1 (Dmo4 LOD = 7.16, for postprandial glucose level) and the other on chromosome X (Dmo11/Odb1: LOD = 7.81, for postprandial glucose level). These data are comparable to results of our previous studies of the OLETF rat.

摘要

为了确定与非胰岛素依赖型糖尿病(NIDDM)相关的遗传决定因素,我们使用大冢长崎德岛肥胖(OLETF)大鼠的359个回交后代进行了全基因组数量性状基因座(QTL)分析。OLETF品系是一种经过充分研究的肥胖NIDDM动物模型,具有高胰岛素血症、高血糖、胰岛素抵抗和大量腹部脂肪等特征。我们用218个标记进行的广泛基因组扫描揭示了9个显著的QTL,包括1号染色体上肥胖的一个强决定因素(Dmo1:LOD = 13.99,针对体重)。发现了两个与葡萄糖稳态高度相关的QTL,一个在1号染色体上(Dmo4 LOD = 7.16,针对餐后血糖水平),另一个在X染色体上(Dmo11/Odb1:LOD = 7.81,针对餐后血糖水平)。这些数据与我们之前对OLETF大鼠的研究结果相当。

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