Chromosome 2 locus Nidd5 has a potent effect on adiposity in the TSOD mouse
Chromosome 2 locus Nidd5 has a potent effect on adiposity in the TSOD mouse
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DOI：
10.1007/s00335-005-0161-5
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发表时间：
2006-05-01
期刊：
影响因子：
2.5
通讯作者：
Izumi, Tetsuro
中科院分区：
文献类型：
--
作者：
Mizutani, Shin;Gomi, Hiroshi;Izumi, Tetsuro
我们之前报道了 TSOD（津村、铃木、肥胖糖尿病）小鼠（多基因肥胖 2 型糖尿病模型）2 号染色体上体重、非胰岛素依赖型糖尿病 5 (Nidd5) 的数量性状基因座。为了找到负责发病机制特定组成部分的基因，我们使用标记辅助选择方案来产生同源菌株。这些小鼠被设计为携带对照 BALB/cA 衍生的基因组间隔和 TSOD 背景以寻找表型的丢失。与 TSOD 小鼠相比，同系间隔最宽的品系之一 D2Mit297-D2Mit304 的体重和肥胖程度均有所下降。其他同源菌株的表型分析进一步缩小了 D2Mit433 和 D2Mit91 之间 9.4 Mb 间隔的位点，之前已在该位点周围绘制了许多体重和肥胖的位点。尽管该基因座对体重的影响相对较小，但它对脂肪量有重大影响，这解释了亲本 TSOD 和 BALB/cA 小鼠之间脂肪指数差异的大约 60%。此外，与对照同窝动物相比，具有最小 BALB/cA 衍生区域的同类品系显示出白色和棕色脂肪细胞的细胞尺寸显着更小。然而，该位点主要并不影响食物消耗、一般活动或冷暴露后的直肠温度，尽管亲本菌株之间在这些性状上存在明显差异。目前的工作从物理上描绘了 TSOD 小鼠肥胖的主要部位。
We previously reported a quantitative trait locus for body weight, non-insulin-dependent diabetes 5 (Nidd5), on Chromosome 2 in the TSOD (Tsumura, Suzuki, Obese Diabetes) mouse, a model of polygenic obese type 2 diabetes. To find the gene responsible for a specific component of the pathogenesis, we used a marker-assisted selection protocol to produce congenic strains. These mice are designed to carry a control BALB/cA-derived genomic interval and a TSOD background to look for loss of phenotype. One of the strains with the widest congenic interval, D2Mit297-D2Mit304, showed reductions in both body weight and adiposity compared with TSOD mice. The phenotypic analyses of other congenic strains further narrowed the locus in a 9.4-Mb interval between D2Mit433 and D2Mit91, around which numerous loci for body weight and adiposity have been mapped previously. Although the locus showed a relatively modest effect on body weight, it had a major influence on fat mass that explains approximately 60% of the difference in the adipose index between parental TSOD and BALB/cA mice. Furthermore, the congenic strain with a minimal BALB/cA-derived region showed significantly smaller cell sizes of white and brown adipocytes compared with the control littermates. However, the locus did not primarily affect food consumption, general activity, or rectal temperature after cold exposure, although there are clear differences in these traits between the parental strains. The present work physically delineates the major locus for adiposity in the TSOD mouse.