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| CLONING AND GENE DEFECTS IN MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN ASSOCIATED WITH ABETALIPOPROTEINEMIA |
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| Author(s): SHARP D, BLINDERMAN L, COMBS KA, KIENZLE B, RICCI B, WAGERSMITH K, GIL CM, TURCK CW, BOUMA ME, RADER DJ, AGGERBECK LP, GREGG RE, GORDON DA, WETTERAU JR |
| Source: NATURE Volume: 365 Issue: 6441 Pages: 65-69 Published: SEP 2 1993 |
| Times Cited: 273 References: 17 |
| Abstract: THE microsomal triglyceride transfer protein (MTP), which catalyses the transport of triglyceride, cholesteryl ester and phospholipid between phospholipid surfaces, is a heterodimer composed of the multifunctional protein, protein disulphide isomerase, and a unique large subunit with an apparent M(r) 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 abetatipoproteinaemia5, a rare autosomal recessive disease characterized by a defect in the assembly or secretion of plasma lipoproteins that contain apolipoprotein 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 abetatipoproteinaemic 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 die large subunit of MTP is the proximal cause of abetalipoproteinaemia in these two subjects, and that MTP is required for the secretion of plasma lipoproteins that contain apolipoprotein B. |
| Document Type: Article |
| Language: English |
Addresses:
1. BRISTOL MYERS SQUIBB, DEPT METAB DIS, PRINCETON, NJ 08543 USA
2. UNIV CINCINNATI, DEPT PHARMACOL & CELL BIOPHYS, CINCINNATI, OH 45267 USA
3. UNIV CALIF SAN FRANCISCO, HOWARD HUGHES MED INST, DEPT MED, SAN FRANCISCO, CA 94143 USA
4. UNIV PARIS 07, INSERM, U327, F-75018 PARIS, FRANCE
5. NHLBI, MOLEC DIS BRANCH, BETHESDA, MD 20892 USA
6. CNRS, CTR GENET MOLEC, F-91198 GIF SUR YVETTE, FRANCE |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: LV646 |
| ISSN: 0028-0836 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |