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在因致死性染色体缺失而纯合的小鼠中肝细胞膜蛋白的选择性表达

Selective expression of hepatocellular membrane proteins in mice homozygous for a lethal chromosomal deletion.

作者信息

Wolkoff A W, Stockert R J

出版信息

Proc Soc Exp Biol Med. 1986 Feb;181(2):270-4. doi: 10.3181/00379727-181-42252.

Abstract

Previous studies of mice homozygous for one of several overlapping radiation-induced deletions in chromosome 7 revealed reduced expression of a number of hepatocyte proteins. These proteins include the plasma membrane receptors for insulin, epidermal growth factor, and glucagon, all of which are reduced in number by over 70% with no change in apparent affinity constants. It is not known whether all or only select liver cell surface proteins are so affected in newborn deletion homozygotes. In the present study, we investigated expression of two additional, functionally distinct intrinsic hepatocellular membrane binding proteins: the hepatic binding protein (HBP: the receptor for asialoglycoproteins), and the organic anion binding protein (OABP) which may play a role in organic anion transport. Immunoblot analysis showed the content of OABP and HBP in neonatal mutants to be identical to that in controls. As compared to adults, neonates showed levels of only about 8% of HBP and 75% of OABP binding proteins. Assays of HBP binding activities confirmed these results. The normal levels of these hepatocyte binding proteins in the deletion homozygotes suggest that the DNA sequences deleted in these mutants do not regulate all genes encoding such proteins but only a selected number of them.

摘要

先前对7号染色体上几个重叠的辐射诱导缺失之一的纯合小鼠的研究表明,一些肝细胞蛋白的表达减少。这些蛋白包括胰岛素、表皮生长因子和胰高血糖素的质膜受体,所有这些受体的数量均减少了70%以上,而表观亲和常数没有变化。目前尚不清楚在新生的缺失纯合子中,所有肝细胞表面蛋白还是只有部分肝细胞表面蛋白受到如此影响。在本研究中,我们研究了另外两种功能不同的肝细胞内在膜结合蛋白的表达:肝结合蛋白(HBP:去唾液酸糖蛋白的受体)和有机阴离子结合蛋白(OABP),后者可能在有机阴离子转运中起作用。免疫印迹分析表明,新生突变体中OABP和HBP的含量与对照相同。与成年小鼠相比,新生小鼠中HBP和OABP结合蛋白的水平仅约为成年小鼠的8%和75%。HBP结合活性测定证实了这些结果。缺失纯合子中这些肝细胞结合蛋白的正常水平表明,这些突变体中缺失的DNA序列并不调控所有编码此类蛋白的基因,而只调控其中一部分选定的基因。

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