Ross R S, Gregg R E, Law S W, Monge J C, Grant S M, Higuchi K, Triche T J, Jefferson J, Brewer H B
Molecular Disease Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.
J Clin Invest. 1988 Feb;81(2):590-5. doi: 10.1172/JCI113357.
apoB DNA, RNA, and protein from two patients with homozygous hypobetalipoproteinemia (HBL) were evaluated and compared with normal individuals. Southern blot analysis with 10 different cDNA probes revealed a normal gene without major insertions, deletions, or rearrangements. Northern and slot blot analyses of total liver mRNA from HBL patients documented a normal size apoB mRNA that was present in greatly reduced quantities. ApoB protein was detected within HBL hepatocytes utilizing immunohistochemical techniques; however, it was markedly reduced in quantity when compared with control samples. No apoB was detectable in the plasma of HBL individuals with an ELISA assay. These data are most consistent with a mutation in the coding portion of the apoB gene in HBL patients, leading to an abnormal apoB protein and apoB mRNA instability. These results are distinct from those previously noted in abetalipoproteinemia, which was characterized by an elevated level of hepatic apoB mRNA and accumulation of intracellular hepatic apoB protein.
对两名纯合子低β脂蛋白血症（HBL）患者的载脂蛋白B（apoB）DNA、RNA和蛋白质进行了评估，并与正常个体进行了比较。用10种不同的cDNA探针进行Southern印迹分析，结果显示基因正常，无主要插入、缺失或重排。对HBL患者肝脏总mRNA进行Northern印迹和狭缝印迹分析，结果表明apoB mRNA大小正常，但数量大幅减少。利用免疫组化技术在HBL肝细胞中检测到了apoB蛋白；然而，与对照样品相比，其数量明显减少。用ELISA检测法在HBL个体的血浆中未检测到apoB。这些数据与HBL患者apoB基因编码区的突变最为一致，该突变导致apoB蛋白异常和apoB mRNA不稳定。这些结果与先前在无β脂蛋白血症中观察到的结果不同，无β脂蛋白血症的特征是肝脏apoB mRNA水平升高和细胞内肝脏apoB蛋白积累。
