Genetic dissection of susceptibility genes for diabetes and related phenotypes on mouse chromosome 14 by means of congenic strains.
Genetic dissection of susceptibility genes for diabetes and related phenotypes on mouse chromosome 14 by means of congenic strains.
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DOI：
10.1186/s12863-014-0093-8
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发表时间：
2014-08-29
期刊：
影响因子：
2.9
通讯作者：
Ikegami H
中科院分区：
文献类型：
--
作者：
Babaya N;Ueda H;Noso S;Hiromine Y;Itoi-Babaya M;Kobayashi M;Fujisawa T;Ikegami H
2 型糖尿病的易感位点 Nidd2n 已被定位到小鼠 14 号染色体 (Chr 14)，并使用名古屋柴田安田 (NSY) 小鼠（一种自发性 2 型糖尿病动物模型）的染色体品系 (C3H-Chr 14NSY) 进行了确认。本研究的目的是定位和表征 Nidd2n。我们在对照 C3H/HeNcrj (C3H) 背景上构建了两个 NSY-Chr 14 不同片段纯合的新同源菌株：R1 (C3H.NSY-(D14Mit206-D14Mit5)) 拥有近端和中间片段，R2 (C3H.NSY-(D14Mit206-D14Mit186)) 拥有最近端片段NSY-Chr 14。与共体 C3H-Chr 14NSY (R0) 以及亲本 NSY 和 C3H 菌株进行比较，研究了糖尿病相关表型。同源 R1 和 R2 的攻击后血糖显着高于 C3H 小鼠。相反，R1 和 R2 小鼠的空腹血糖显着低于 C3H 小鼠。与 C3H 小鼠相比，R1 和 R2 小鼠的胰岛素敏感性显着受损。 R2 的体重和脂肪垫重量显着高于 C3H 和 R1。 R0、R1和R2的瘦素水平显着高于C3H小鼠，其中R2的水平最高，与NSY小鼠相似。 R0、R1和R2小鼠血清脂联素水平显着低于C3H小鼠，而NSY小鼠血清脂联素水平显着高于C3H小鼠。这些数据表明 Chr 14 含有多个与糖尿病相关表型的基因。最初的Nidd2n位于Chr 14的中间区域，被分为两段； Nidd2.1n 位于近端 Chr 14 中，Nidd2.2n 位于远端 Chr 14 中。Nidd2.1n 会导致攻击后高血糖、胰岛素抵抗和肥胖。 Nidd2.2n 会导致禁食以及挑战后高血糖和胰岛素抵抗。 Adp1n 被定位在中段，它有助于减少肥胖和增加胰岛素敏感性，而不是导致糖尿病的基因。
A susceptibility locus, Nidd2n, for type 2 diabetes has been mapped to mouse chromosome 14 (Chr 14) and confirmed using the consomic strain (C3H-Chr 14NSY) of the Nagoya-Shibata-Yasuda (NSY) mouse, an animal model of spontaneous type 2 diabetes. The aim of this study was to localize and characterize Nidd2n. We constructed two novel congenic strains homozygous for different segments of NSY-Chr 14 on the control C3H/HeNcrj (C3H) background: R1 (C3H.NSY-(D14Mit206-D14Mit5)) possesses the proximal and middle segment, and R2 (C3H.NSY-(D14Mit206-D14Mit186)) possesses the most proximal segment of NSY-Chr 14. Diabetes-related phenotypes were studied in comparison with those of consomic C3H-Chr 14NSY (R0) and parental NSY and C3H strains. Congenic R1 and R2 showed significantly higher post-challenge glucose than that in C3H mice. Fasting glucose, in contrast, was significantly lower in R1 and R2 than in C3H mice. Insulin sensitivity was significantly impaired in R1 and R2 compared to C3H mice. R2 showed significantly higher body weight and fat-pad weight than those in C3H and R1. Leptin level was significantly higher in R0, R1 and R2 than in C3H mice, with R2 showing the highest level, similar to that in NSY mice. Serum adiponectin level was significantly lower in R0, R1 and R2 than in C3H mice, while it was significantly higher in NSY than in C3H mice. These data indicate that Chr 14 harbors multiple genes for diabetes-related phenotypes. The original Nidd2n, which is located in the middle region of Chr 14, was divided into two segments; Nidd2.1n in proximal Chr 14 and Nidd2.2n in distal Chr 14. Nidd2.1n contributes to post-challenge hyperglycemia, insulin resistance and adiposity. Nidd2.2n contributes to fasting as well as post-challenge hyperglycemia and insulin resistance. Adp1n, which contributes to decreased adiposity and increased insulin sensitivity, rather than a diabetogenic gene, was mapped in the middle segment.
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