| First Author | Kim E | Year | 1998 |
| Journal | J Clin Invest | Volume | 101 |
| Issue | 6 | Pages | 1468-77 |
| PubMed ID | 9502790 | Mgi Jnum | J:46549 |
| Mgi Id | MGI:1201298 | Citation | Kim E, et al. (1998) Dual mechanisms for the low plasma levels of truncated apolipoprotein B proteins in familial hypobetalipoproteinemia. Analysis of a new mouse model with a nonsense mutation in the Apob gene. J Clin Invest 101(6):1468-77 |
| abstractText | Familial hypobetalipoproteinemia (FHbeta), a syndrome characterized by low plasma cholesterol levels, is caused by mutations in the apo-B gene that interfere with the synthesis of apo-B100. FHbeta mutations frequently lead to the synthesis of a truncated form of apo-B, which typically is present in plasma at < 5% of the levels of apo-B100. Although many FHbeta mutations have been characterized, the basic mechanisms causing the low plasma levels of truncated apo-B variants have not been defined. We used gene targeting to create a mutant allele that exclusively yields a truncated apo-B, apo-B83. In mice heterozygous for the Apob83 allele, plasma levels and the size and density distribution of apo-B83-containing lipoproteins were strikingly similar to those observed in humans with FHbeta and an apo-B83 mutation. Analysis of mice carrying the Apob83 mutation revealed two mechanisms for the low plasma levels of apo-B83. First, Apob83 mRNA levels and apo-B83 secretion were reduced 76 and 72%, respectively. Second, apo-B83 was removed rapidly from the plasma, compared with apo-B100. This mouse model provides a new level of understanding of FHbeta and adds new insights into apo-B metabolism. |
