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TY - JOUR AU - Sharp, Daru AU - Blinderman, Laura AU - Combs, Kelly A. AU - Kienzle, Bernadette AU - Ricci, Beverly AU - Wager-Smith, Karen AU - Gil, Cleris M. AU - Turck, Christoph W. AU - Boumas, Marie-Elizabeth AU - Rader, Daniel J. AU - Aggerbeck, Lawrence P. AU - Gregg, Richard E. AU - Gordon, David A. AU - Wetterau, John R. PY - 1993 DA - 1993/09/01 TI - Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia JO - Nature SP - 65 EP - 69 VL - 365 IS - 6441 AB - 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. SN - 1476-4687 UR - https://doi.org/10.1038/365065a0 DO - 10.1038/365065a0 ID - Sharp1993 ER -