应用体细胞基因转移技术建立的遗传性极度高血脂小鼠模型

目的　利用体细胞脂蛋白脂酶 (lipoproteinlipase ,LPL)有益变异体基因转移方法 ,救治原本在出生后两天内全部死亡的LPL基因敲除纯合子小鼠。方法　以腺病毒为载体 ,在初生小鼠肌肉内表达LPL基因有益突变体 ,观察救治存活后成年动物的表型变化。结果　本法救治纯合子小鼠的成功率达到 75 % ,大大高于以野生型LPL基因救治的国外研究。存活的成年纯合子小鼠表现为极度高脂血症。结论　利用LPL基因突变体进行体细胞基因转移可成功救治LPL基因敲除纯合子小鼠 ,并建立了极度高脂血症动物模型。

Rescue of a Lethal Mouse Model of Extreme Hypertriglyceridimia by Somatic Gene Transfer of a Beneficial LPL Mutant Gene

Objective To rescue homozygous (LO) lipoprotein lipase (LPL) knockout mice that should have died in 48 hours after birth by somatic gene transfer using a beneficial mutant of LPL gene (LPL447). Method A recombinant adenoviral vector expressing LPL447 was delivered to the neonatal mice by intramuscular route. The phenotypes of rescued mice were analyzed. Results 75% of LO mice survived the entire suckling period and lived for up to normal adulthood, which is greatly higher than the survival rate achieved by other groups abroad using wild type LPL gene. Adult LO mice exhibited extremely high triglyceride levels.Conclusion Adenovirus mediated LPL447 gene transfer during neonatal stage can rescue the LO mice successfully. Adult LO mice can be used as a severe hyperlipemia animal model for further investigation.