【摘要】 目的 建立核异质核糖核蛋白U（hnRNP U）基因全身性敲除小鼠模型，研究该基因在小鼠体内的功能。方法 通过同源重组的方法建立hnRNP U全身性敲除的小鼠模型。观察统计小鼠的出生以及生长情况，检查其组织器官发育，通过代谢笼检测其代谢水平，并用糖耐量试验检测其糖代谢变化。结果 hn RNP U全身性敲除纯合子小鼠(Hnrnpu^-/-)死于胚胎期7.5 d前，而其杂合子小鼠也有部分在胚胎期死亡，出生的杂合子小鼠表现为生长发育迟缓、部分组织的重量减轻、骨密度降低以及肌肉含量减少。进一步实验表明，Hnrnpu^+/-小鼠夜间进食量、活动水平和产热量等降低，糖代谢能力下降。结论 通过同源重组方法成功建立hnRNP U全身性敲除小鼠模型，并在整体水平证实了该基因在小鼠发育和代谢稳态调节中起重要作用。更多还原

【Abstract】 Objective To establish a heterogeneous nuclear ribonucleoprotein U（HnRNP U） knockout mouse model and study the roles of hnRNP U in vivo. Methods The Hnrnpu conventional knockout mouse model was established by homologous recombination. The roles of hnRNP U in vivo were studied by growth analyses, body and tissues weighting, metabolic analyses and glucose tolerance tests.Results The Hnrnpu^-/-mice are embryonic leathal before embryonic day 7.5. The Hnrnpu^+/-mice were partially died at embryonic stage and the viable individuals showed growth retardation with decreased tissues weight, bone mineral density and lean mass compared with wild-type littermates. In addition,hnRNP U haploinsufficiency leads to decreased activity and food intake at night and impaired glucose homeostasis. Conclusion Hnrnpu knockout mouse model was successfully established and hnRNP U played a great role in a diverse group of cellular processes, including the normal growth of somatic tissues, metabolic activities and glucose metabolism.更多还原