混合性高甘油三酯/高胆固醇血症小鼠模型的培育

目的通过脂蛋白脂酶（lipoprotein lipase，LPL）基因敲除极度高甘油三酯血症小鼠LPLO与ApoE基因敲除高胆固醇血症小鼠ApoEO杂交，产生混合性高甘油三酯／高胆固醇血症小鼠模型LPLO／ApoEO。方法采用杂交、回交、互交的方法进行培育，并以重组腺病毒为载体在初生小鼠四肢肌肉内表达LPL基因有益突变体LPL447，救治出生2d内即死亡LPLO／ApoEO纯合子初生小鼠。采用从LPLO，ApoEO小鼠的个体组织（鼠尾）中提取基因组DNA进行PCR分析和血浆脂质检测个体基因型。结果LPL基因有益突变体在纯合子小鼠体内短暂表达，能够成功救治LPLO／ApoEO双基因敲除小鼠。成年小鼠表现为极度的混合性高脂血症，其血浆甘油三酯和胆固醇水平分别是正常小鼠的76和14倍。结论成功培育了LPLO／ApoEO双基因敲除的遗传性混合性高甘油三酯、高胆固醇血症小鼠模型。

Development of Combined Hypercholesterolemic/ Hypertriglyceridemic Mouse Model

Objective To establish a combined hypercholesterolemic/hypertriglyceridemic mouse model by cross-breeding of LPL and ApoE knockout mice. Methods The model was developed by crossbred, backcross and intercross of the 2 lines of knockout mice, and rescued by muscular expression of a LPL beneficial mutant in homozygous neonates. The genotype was determined by PCR and confirmed by blood lipid assay. Results The LPL and ApoE double knockout mice could be rescued by muscular expression of LPL. Plasma TG and TC levels in adult LPLO/ApoEO mice were increased 76 and 14 fold, respectively, compared with wild-type littermates. Conclusion hypercholesterolemic/hypertriglyceridemic mouse model has been developed successfully.