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Analysis of the apolipoprotein B gene and messenger ribonucleic acid in abetalipoproteinemia.

The apolipoprotein B-100 (apoB-100) gene in leukocytes and the apoB-100 messenger RNA (mRNA) and translated apolipoprotein in the livers from normal and abetalipoproteinemic individuals were evaluated. Four complementary DNA probes for apoB-100 covering the 5', middle, and 3' regions of the apoB-100 mRNA were utilized and Southern blot analysis indicated that the apoB-100 gene is present in abetalipoproteinemia without major insertions or deletions. Polyadenylated hepatic apoB-100 mRNA from two abetalipoproteinemic patients was normal in size, and the concentration of apoB-100 mRNA was increased sixfold compared with control hepatic apoB-100 mRNA levels. ApoB-100 was detected in hepatocytes of abetalipoproteinemic patients by immunohistochemical techniques. These results indicate that the biochemical defect in abetalipoproteinemic patients studied is most consistent with a posttranslational defect in apoB-100 processing or secretion with an up-regulation of the apoB-100 mRNA.