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Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia

Abstract

THE microsomal triglyceride transfer protein (MTP), which catalyses the transport of triglyceride, cholesteryl ester and phospho-lipid between phospholipid surfaces, is a heterodimer composed of the multifunctional protein, protein disulphide isomerase, and a unique large subunit with an apparent Mr of 88K (refs 1–3). It is isolated as a soluble protein from the lumen of the microsomal fraction of liver and intestine4. The large subunit of MTP was not detectable in four unrelated subjects with abetalipoproteinaemia5, a rare autosomal recessive disease characterized by a defect in the assembly or secretion of plasma lipoproteins that contain apolipo-protein B (ref. 6). We report here the isolation and sequencing of complementary DNA encoding the large subunit of MTP. A comparison of this sequence to corresponding genomic sequences from two abetalipoproteinaemic subjects revealed a homozygous frameshift mutation in one subject and a homozygous nonsense mutation in the other. The results indicate that a defect in the gene for the large subunit of MTP is the proximal cause of abetalipopro-teinaemia in these two subjects, and that MTP is required for the secretion of plasma lipoproteins that contain apolipoprotein B.

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Sharp, D., Blinderman, L., Combs, K. et al. Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia. Nature 365, 65–69 (1993). https://doi.org/10.1038/365065a0

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