富含亮氨酸重复序列的G蛋白偶联受体4基因缺陷导致寿命缩短和多器官组织衰老

目的:研究富含亮氨酸重复序列的G蛋白偶联受体4(LGR4)基因缺失对小鼠寿命以及衰老相关表型的影响。方法:在正常繁殖、饲养状态下,观察LGR4基因敲除小鼠与衰老相关的表型,并记录每只小鼠的出生时间和死亡时间,比较LGR4基因敲除小鼠与正常小鼠的自然寿命差异;此外,收集2组老年小鼠的不同组织(如皮肤、眼睛、肺脏、肝脏、脾脏等),进行病理切片和苏木精-伊红(HE)染色,观察各组织形态学改变。结果:LGR4基因敲除小鼠中位生存期为17.25个月,野生型小鼠中位生存期为22.75个月,2组生存率存在明显差异(P20个月的2组小鼠生存率并无统计学差异。组织学结果提示,老龄LGR4基因敲除小鼠的皮肤出现明显的结构异常,包括角质层不平整、毛囊稀少、皮下脂肪层变薄、血管减少。结论:LGR4基因缺失缩短小鼠的全程寿命,但并不影响老龄小鼠的生存率。

Leucine-rich repeat-containing G-protein coupled receptor 4 gene deficiency leads to reduction of lifespan and aging of multiple organs

Objective To study the effect of leucine-rich repeat-containing G-protein coupled receptor 4 （LGR4） gene deficiency on life-span and aging-related phenotype of mice. Methods Life-span and aging-related phenotype of LGR4 gene knockout mice （81 males and 97 females） and wild-type mice （70 males and 82 females） under the same feeding and breeding condition were compared. The morphology changes of various tissues were studied with hematoxylin- eosin staining and compared. Results Median survival period of LGR4 knockout mice was 17.25 months , while the median survival period of wild-type mice was 22.75 months. The survival rate were significant difference between the 2 groups （P〈0.001）. However, the survival rate of aging mice of both groups did not show any difference. LGR4 knockout mice showed obvious atrophy changes of skin. Conclusions LGR4 deficiency decreased the life span of mice, but did not affect the survival of aging mice.