| First Author | Chen Z | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 16 | Pages | 14135-45 |
| PubMed ID | 11839763 | Mgi Jnum | J:76047 |
| Mgi Id | MGI:2178460 | Doi | 10.1074/jbc.M200617200 |
| Citation | Chen Z, et al. (2002) Hypobetalipoproteinemic Mice with a Targeted Apolipoprotein (Apo) B-27.6-specifying Mutation. IN VIVO EVIDENCE FOR AN IMPORTANT ROLE OF AMINO ACIDS 1254-1744 OF ApoB IN LIPID TRANSPORT AND METABOLISM OF THE ApoB-CONTAINING LIPOPROTEIN. J Biol Chem 277(16):14135-45 |
| abstractText | Carboxyl-terminal deletion of apoB-100 may impair its triglyceride (TG)-transporting capability and alter its catabolism. Here, we compare our newly generated apoB gene (Apob)-targeted apoB-27.6-bearing mice to our previously reported apoB-38.9 mice to understand further the relationship between the size of a truncated apoB variant and its function/metabolism in vivo. The apoB-27.6-specifying mutation produces a premature stop codon six amino acids (aa) downstream of the last codon of mouse Apob exon 24 (corresponding to aa 1254 of human apoB-100). ApoB-27.6 transcripts were 3- and 5-fold more abundant than apoB wild type and apoB-38.9 transcripts in the liver. Likewise, hepatic secretion rates of apoB-27.6 were 7-fold higher than those of apoB-48 and apoB-38.9. In contrast, apoB-27.6 heterozygotes (Apob(27.6/+)) had lower hepatic TG secretion rates and higher liver TG contents than both apoB-38.9 heterozygotes (Apob(38.9/+)) and apoB wild type mice (Apob(+/+)). ApoB-27.6 was secreted by Apob(27.6/+) hepatocytes as dense high density lipoprotein particles. Moreover, despite its high secretion rates, apoB-27.6 was barely detectable in plasma. Disruption of apoE gene in Apob(38.9/+) and Apob(27.6/+) dramatically increased plasma levels of apoB-38.9 as well as apoB-48 but caused no change in plasma apoB-27.6 concentrations. Finally, the birth rate of apoB-27.6 homozygotes (Apob(27.6/27.6)) from intercrosses of Apob(27.6/+) was 7-fold lower than that of Apob(38.9/38.9) from Apob(38.9/+) intercrosses (1.8% versus 12%). Crossbreeding of Apob(27.6/27.6) and Apob(38.9/38.9) produced viable Apob(27.6/38.9) offspring, but Apob(27.6/27.6) intercrosses produced no offspring. Together, these results demonstrate in vivo that the apoB-27.6-apoB-38.9 peptide segment (aa 1254-1744) plays a critical role, not only in supporting hepatic TG-secretion and in modulating catabolism of apoB-containing lipoproteins, but also in normal mouse embryonic development. |
