人类p93基因转基因小鼠模型的建立及功能初探

目的 探讨心肌特异性表达的新激酶基因p93对心脏发育的影响.方法 构建携带人心肌特异启动子的α-MHC-p93转基因质粒,以显微注射法获得p93转基因首建鼠.对转基因小鼠进行形态学观察及血清水平检测.结果 成功构建了携带有人p93基因的真核表达载体α-MHC-p93,获得首建鼠7只.经繁育共获得F1、F2代转基因鼠234只,筛选出转基因阳性鼠4只,其中F1代3只,F2代1只.小鼠心脏大体形态学检测未见房室间隔缺损现象.血清学检测结果显示:p93转基因阳性鼠血Ca2+水平明显高于正常对照组[ (28±1)mg/L比(26±1)mg/L,P＜0.05],差异有统计学意义(P＜0.05)；血清肌酸激酶同工酶(CK-MB)水平低于正常对照组[(624.7±268.1)U/L比(1229.8±532.4)U/L,P＜0.05]；血清乳酸脱氢酶(LDH)水平及心脏质量指数(HMI)与正常对照组相比,差异无统计学意义.结论 成功建立了人p93基因的转基因小鼠模型.单一转入p93基因没有造成实验动物的房室间隔缺损及心肌肥大.

Human gene p93 transgenic mouse model and its function exploration

Objective To explore the role of p93 gene in heart development and heart diseases.Methods The recombined α-myosin heary chain ( α-MHC-p93 ) vector was constructed and a model of Founder transgenic mice was established by microinjection.The integration and heredity of the foreign gene were tested by poly meras chain reaction(PCR) and Southern blotting.The phenotype and the serum level were performed to observe the function of p93 gene in transgenic mice.Results The plasmid vector namelyα-MHC-p93 was constructed successfully.PCR and Southern blotting results showed that 3 of the F1 and 1 of F2 transgenic mice were positive with p93 gene.Observing the phenotype of p93 transgenic mouse model did not detect the atrioventricular septal defect (AVSD).The myocardial zymogram of p93 transgenic mice serum was abnormal,especially Ca2 + and creatine kinase isoenzyme.The abnormality was significantly different from the normal group (P ＜0.05 ).There were no significant differences between the p93 transgenic mice and normal group by heart mass index (HMI) measure. Conclusions The transgenic mouse model carrying p93 gene can be established.Single p93 gene does not induce AVSD and cardiac hypertrophy and may protect the heart.