Kayo T, Fujita H, Nozaki J, E X, Koizumi A
Department of Hygiene, Akita University School of Medicine, Japan.
Comp Med. 2000 Jun;50(3):296-302.
Our objective was to map the genes responsible for poor glucose tolerance in a C57BL/6 (B6) mouse model, which provides a human model of non-insulin-dependent diabetes mellitus. Insulin secretion was found to be significantly lower in B6 than in C3H/He (C3H) mice (analysis of variance, P < 0.05) at 10, 20, and 30 minutes during the intraperitoneal glucose tolerance test (IPGTT: 1.5 g glucose/kg of body weight).
Mean 30-minute blood glucose values during IPGTT at 8, 9, and 10 weeks of age were used as a surrogate for glucose tolerance. The primers of 87 genetic microsatellite markers (14.9 +/- 6.2 cM apart) genome-wide quantitative trait linkage (QTL) analysis in F2 and F3 mice with the highest and lowest (n = 15 for each extreme) 30-minute blood glucose values were used.
Genome-wide QTL analysis confirmed the locus (D2Mit48) on chromosome 2, with a LOD score of 8.3, and the locus (D13Mit48) on chromosome 13, with a LOD score of 4.2 in F3. Direct sequencing of candidate genes, proprotein convertase-2 (PC2) on chromosome 2 and proprotein convertase-1/3 (PC1/PC3) on chromosome 13, failed to reveal a mutation or polymorphism specific to B6 mice.
Use of QTL mapping revealed two loci associated with poor glucose tolerance of B6.
我们的目标是在C57BL/6（B6）小鼠模型中定位导致葡萄糖耐量不良的基因，该模型可提供非胰岛素依赖型糖尿病的人类模型。在腹腔葡萄糖耐量试验（IPGTT：1.5 g葡萄糖/千克体重）的10、20和30分钟时，发现B6小鼠的胰岛素分泌显著低于C3H/He（C3H）小鼠（方差分析，P < 0.05）。
将8、9和10周龄IPGTT期间30分钟的平均血糖值用作葡萄糖耐量的替代指标。使用在F2和F3小鼠中进行全基因组数量性状连锁（QTL）分析的87个遗传微卫星标记（相距14.9 +/- 6.2 cM）的引物，这些小鼠具有最高和最低（每个极端各n = 15）的30分钟血糖值。
全基因组QTL分析证实了F3中位于2号染色体上的位点（D2Mit48），LOD得分为8.3，以及位于13号染色体上的位点（D13Mit48），LOD得分为4.2。对候选基因，即2号染色体上的前蛋白转化酶-2（PC2）和13号染色体上的前蛋白转化酶-1/3（PC1/PC3）进行直接测序，未发现B6小鼠特有的突变或多态性。
使用QTL定位揭示了两个与B6小鼠葡萄糖耐量不良相关的位点。
