Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2 sterol carrier protein-x gene function

被引:242
作者
Seedorf, U [1 ]
Raabe, M
Ellinghaus, P
Kannenberg, F
Fobker, M
Engel, T
Denis, S
Wouters, F
Wirtz, KWA
Wanders, RJA
Maeda, N
Assmann, G
机构
[1] Univ Munster, Inst Arteriosclerosis Res, D-48129 Munster, Germany
[2] Univ Munster, Inst Clin Chem & Lab Med, Zent Lab, D-48129 Munster, Germany
[3] Univ Amsterdam, Acad Med Ctr, Dept Pediat, NL-1105 AZ Amsterdam, Netherlands
[4] Univ Utrecht, Ctr Biomembranes & Lipid Enzymol, Utrecht, Netherlands
[5] Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA
关键词
gene targeting; peroxisomes; beta-oxidation; Refsum disease; cholesterol; steroid hormones;
D O I
10.1101/gad.12.8.1189
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1189 / 1201
页数:13
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