Center for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.
Department of Psychiatry, UT Southwestern Medical Center, Dallas, Texas, USA.
Obesity (Silver Spring). 2023 Jun;31(6):1644-1654. doi: 10.1002/oby.23766. Epub 2023 May 10.
Prader-Willi syndrome (PWS) is a multisystem genetic disorder. Unfortunately, none of several mouse models carrying PWS mutations emulates the entirety of the human PWS phenotype, including hyperphagia plus obesity.
To determine whether housing at thermoneutrality (TN, 30 °C) permits the development of hyperphagia and obesity in the Snord116del PWS mouse model, the effects of housing three different ages of Snord116del and wild-type (WT) littermates at TN versus room temperature (RT, 22-24 °C) for 8 weeks were compared.
Snord116del mice born and maintained at TN exhibited lower body weight curves, lower percentage fat mass, and lower food intake than WT mice at RT. In 4- to 6-month-old high-fat diet-fed female mice, TN raised the Snord116del body weight curve closer to that of RT-housed WT mice although the TN-housed Snord116del mice did not gain more adiposity or exhibit greater food intake. In 6- to 8-month-old high-fat diet-fed male mice, body weight, adiposity, and food intake of TN-housed Snord116del mice remained far below levels in RT-housed WT mice. TN elicited hypotonia in Snord116del adults and exacerbated mortality of Snord116del newborns.
In none of three tested TN protocols were greater food intake, body weight, or adiposity induced in Snord116del mice compared with RT-housed WT mice.
普拉德-威利综合征(PWS)是一种多系统遗传疾病。遗憾的是,几种携带 PWS 突变的小鼠模型均无法模拟人类 PWS 表型的全部特征,包括多食症伴肥胖。
为了确定在热中性(TN,30°C)环境中饲养是否会导致 Snord116del PWS 小鼠模型出现多食症和肥胖,比较了在 TN(30°C)和室温(RT,22-24°C)下分别饲养不同年龄的 Snord116del 和野生型(WT)同窝仔鼠 8 周的效果。
在 TN 环境中出生和维持的 Snord116del 小鼠的体重曲线、体脂百分比和食物摄入量均低于 RT 环境中的 WT 小鼠。在 4-6 月龄高脂肪饮食喂养的雌性小鼠中,TN 使 Snord116del 的体重曲线更接近 RT 环境中饲养的 WT 小鼠,尽管 TN 环境中饲养的 Snord116del 小鼠并未增加更多的体脂或表现出更高的食物摄入量。在 6-8 月龄高脂肪饮食喂养的雄性小鼠中,TN 环境中饲养的 Snord116del 小鼠的体重、体脂和食物摄入量仍远低于 RT 环境中饲养的 WT 小鼠。TN 导致 Snord116del 成年小鼠出现张力减退,并加重了 Snord116del 新生仔鼠的死亡率。
在三种测试的 TN 方案中,Snord116del 小鼠的食物摄入量、体重或体脂均未高于 RT 环境中饲养的 WT 小鼠。