METHODS: Human cholesteryl ester transfer protein (CETP), a plasma lipid transfer protein not found in mice that reduces HDL-C, and/or its optimal adapter protein human apolipoprotein B (ApoB), were overexpressed in Dysf mice. Mice received a 2% cholesterol diet from 2 months of age and characterized through ambulatory and hanging functional tests, plasma analyses, and muscle histology.
RESULTS: CETP/ApoB expression in Dysf mice caused reduced HDL-C (54.5%) and elevated ratio of CHOL/HDL-C (181.3%) compared to control Dysf mice in plasma, but without raising CHOL. Compared to the severe muscle pathology found in high CHOL Dysf/ApoE double knockout mice, Dysf/CETP/ApoB mice did not show significant changes in ambulation, hanging capacity, increases in damaged area, collagen deposition, or decreases in cross-sectional area and healthy myofibre coverage.
CONCLUSIONS: CETP/ApoB over-expression in Dysf mice decreases HDL-C without increasing CHOL or exacerbating muscle pathology. High CHOL or nonHDL-C caused by ApoE KO, rather than low HDL-C, likely lead to rodent muscular dystrophy phenotype humanization.
方法:人胆固醇酯转移蛋白(CETP),一种在小鼠中没有发现的降低HDL-C的血浆脂质转移蛋白,和/或其最佳衔接蛋白人载脂蛋白B(ApoB),在Dysf小鼠中过表达。小鼠从2个月大开始接受2%胆固醇饮食,并通过走动和悬挂功能测试进行表征,血浆分析,和肌肉组织学。
结果:与对照Dysf小鼠相比,Dysf小鼠的CETP/ApoB表达导致血浆中HDL-C降低(54.5%)和CHOL/HDL-C比例升高(181.3%),但没有提高CHOL。与在高CHOLDysf/ApoE双敲除小鼠中发现的严重肌肉病理相比,Dysf/CETP/ApoB小鼠在行走中没有表现出显著的变化,悬挂能力,受损面积增加,胶原蛋白沉积,或减少横截面积和健康的肌纤维覆盖率。
结论:Dysf小鼠中CETP/ApoB过表达降低HDL-C而不增加CHOL或加重肌肉病理。ApoEKO引起的高CHOL或非HDL-C,而不是低HDL-C,可能导致啮齿动物肌营养不良表型人源化。