QPRT基因功能缺失对肾脏发育的影响

Effects of QPRT gene loss-of-function on renal development

目的:研究喹啉磷酸核糖基转移酶(quinolinic phosphoribosyl transferase,QPRT)基因功能缺失对胚胎肾脏发育的影响。方法:通过免疫组化确定QPRT在胎鼠肾脏组织的表达;构建QPRT基因缺陷型小鼠模型,取QPRT+/+(WT)型和QPRT-/-(KO)型小鼠的血清进行肾功能检测;称重法计算KO及WT组小鼠的体重、肾脏重量及肾脏系数;用HE染色观察小鼠及其子代肾脏病理组织学变化。结果:在妊娠13 d胎鼠肾脏组织,QPRT在发育中的输尿管芽中强烈表达。在基因敲除小鼠模型中,QPRT-/-小鼠的肾脏系数(肾重/体重)显著低于野生型小鼠(P<0.05),且QPRT-/-小鼠的尿素氮、血肌酐、尿酸水平高于野生型组(P<0.05)。肾脏组织HE染色显示QPRT-/-仔鼠的肾脏实质部位局部呈现蜂窝状囊性扩张;QPRT+/-仔鼠见肾脏皮质间质局灶性疏松水肿;QPRT+/+仔鼠肾脏未见明显病理组织学变化。结论:QPRT基因功能缺失可能影响胚胎肾脏发育。

Objective:To study the effect of functional deletion of quinoline phosphoribosyltransferase(QPRT)gene on fetal kidney development.Methods:The expression of QPRT in fetal mouse kidney tissue was located by immunohistochemistry.The QPRT genedeficient mouse model was constructed,and the serum of QPRT+/+(WT)and QPRT-/-(KO)mice were collected for renal function detection.The body weight,kidney weight and kidney coefficient of KO and WT mice were calculated by weighing method,and the histopathological changes of kidney of mice and their offspring were observed by HE staining.Results:QPRT was strongly expressed in developing ureteral buds in fetal mouse kidney at 13 days of gestation.The kidney coefficient(kidney weight/body weight)of QPRT-/-mice was significantly lower than that of wild-type mice,and the levels of urea nitrogen,serum creatinine and uric acid of QPRT-/-mice were higher than those of wild-type mice(P<0.05).HE staining of kidney tissue showed cellular cystic dilatation in renal parenchyma of QPRT-/-offspring mice,QPRT+/-mice showed focal loose edema of renal cortex and interstitium;QPRT+/+mice showed no obvious histopathological changes in the kidneys.Conclusion:The loss of QPRT gene function may affect fetal kidney development.