Seedorf U, Raabe M, Ellinghaus P, Kannenberg F, Fobker M, Engel T, Denis S, Wouters F, Wirtz K W, Wanders R J, Maeda N, Assmann G
Institute for Arteriosclerosis Research, Westfalian Wilhelms-University, D-48129 M-unster, Germany.
Genes Dev. 1998 Apr 15;12(8):1189-201. doi: 10.1101/gad.12.8.1189.
Gene targeting in mice was used to investigate the unknown function of Scp2, encoding sterol carrier protein-2 (SCP2; a peroxisomal lipid carrier) and sterol carrier protein-x (SCPx; a fusion protein between SCP2 and a peroxisomal thiolase). Complete deficiency of SCP2 and SCPx was associated with marked alterations in gene expression, peroxisome proliferation, hypolipidemia, impaired body weight control, and neuropathy. Along with these abnormalities, catabolism of methyl-branched fatty acyl CoAs was impaired. The defect became evident from up to 10-fold accumulation of the tetramethyl-branched fatty acid phytanic acid in Scp2(-/-) mice. Further characterization supported that the gene disruption led to inefficient import of phytanoyl-CoA into peroxisomes and to defective thiolytic cleavage of 3-ketopristanoyl-CoA. These results corresponded to high-affinity binding of phytanoyl-CoA to the recombinant rat SCP2 protein, as well as high 3-ketopristanoyl-CoA thiolase activity of the recombinant rat SCPx protein.
利用小鼠基因打靶技术来研究编码固醇载体蛋白2（SCP2；一种过氧化物酶体脂质载体）和固醇载体蛋白X（SCPx；SCP2与一种过氧化物酶体硫解酶的融合蛋白）的Scp2的未知功能。SCP2和SCPx的完全缺失与基因表达的显著改变、过氧化物酶体增殖、低脂血症、体重控制受损及神经病变有关。除了这些异常外，甲基支链脂肪酰辅酶A的分解代谢也受损。这种缺陷在Scp2(-/-)小鼠中表现为四甲基支链脂肪酸植烷酸积累高达10倍，从而变得明显。进一步的特征分析表明，基因破坏导致植烷酰辅酶A导入过氧化物酶体的效率低下以及3-酮基植烷酰辅酶A的硫解裂解存在缺陷。这些结果与植烷酰辅酶A与重组大鼠SCP2蛋白的高亲和力结合以及重组大鼠SCPx蛋白的高3-酮基植烷酰辅酶A硫解酶活性相一致。
