A genetic basis for the "Adonis" phenotype of low adiposity and strong bones
A genetic basis for the "Adonis" phenotype of low adiposity and strong bones
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DOI：
10.1096/fj.04-1572fje
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发表时间：
2004-06-01
期刊：
影响因子：
4.8
通讯作者：
Platt, JL
中科院分区：
文献类型：
--
作者：
Johnson, GB;Riggs, BL;Platt, JL
果蝇的Toll受体参与宿主防御和建立机体计划。哺乳动物Toll的同源物Toll样受体（TLRs）被认为仅在宿主防御中起作用。在这里，我们报道了TLR4或CD14 （TLR4的共受体）突变的小鼠具有“理想”的身体计划，包括骨矿物质含量、密度和大小的增加以及体脂的减少。这些突变小鼠寿命长，活动和生育能力正常，没有感染的迹象。与许多圈养的野生型小鼠不同，它们不会变得肥胖。尽管所有小鼠的体脂、骨含量和总体重都会继续增加，但突变型小鼠和野生型小鼠的骨含量和体脂的差异随着年龄的增长而增加。因此，TLR4/CD14复合物的缺陷产生了一种“阿多尼斯”表型，其特征是这种理想的体型，这种功能可能被用于治疗骨质疏松症和肥胖症。
Toll receptors in Drosophila contribute to host defense and establish the body plan. Mammalian homologues of Toll, the Toll-like receptors (TLRs), are thought to function only in host defense. Here, we report that mice harboring mutations in TLR4 or in CD14, a co-receptor for TLR4, have an "ideal" body plan consisting of increased bone mineral content, density, and size as well as decreased body fat. These mutant mice live long lives, have normal activity and fertility, and show no evidence of infection. Unlike many strains of caged wild-type mice, they do not become obese. Although all mice continue to gain body fat, bone content, and overall weight, the difference in bone content and body fat between mutant and wild- type mice increases with age. Thus, defects in TLR4/CD14 complex generate an "Adonis" phenotype, characterized by this ideal body type, and this function could potentially be exploited for the treatment of osteoporosis and obesity.