CELLULAR-DISTRIBUTION OF IRON, TRANSFERRIN, AND FERRITIN IN THE HYPOTRANSFERRINEMIC (HP) MOUSE-BRAIN

CELLULAR-DISTRIBUTION OF IRON, TRANSFERRIN, AND FERRITIN IN THE HYPOTRANSFERRINEMIC (HP) MOUSE-BRAIN
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DOI:
10.1002/cne.903550109
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发表时间:
1995-04-24
影响因子:
2.5
通讯作者:
CONNOR, JR
CONNOR, JR
中科院分区:
医学3区
文献类型:
--
作者:
DICKINSON, TK;CONNOR, JR

文献摘要

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低转铁蛋白血症(Hp)小鼠转铁蛋白(Tf)基因中存在点突变或小缺失,导致前体Tf mRNA剪接缺陷。Hp动物产生< 1%的正常转铁蛋白水平,需要补充血清或纯化的转铁蛋白才能生存。由于缺乏内源性脑转铁蛋白,我们研究了区域和细胞分布的铁和铁调节蛋白(转铁蛋白和铁蛋白)在选定的大脑区域的Hp小鼠。除海马铁染色模式外,Hp脑内铁、转铁蛋白和铁蛋白的区域分布与正常相似。铁、铁蛋白和转铁蛋白的细胞分布在Hp和正常动物之间是相似的。Tf和铁染色的主要细胞类型是少突胶质细胞。定性观察表明,铁染色的细胞数量是相似的Hp和正常小鼠之间,而Hp Tf阳性细胞的数量减少。铁蛋白免疫染色在两种情况下是相似的。然而,铁蛋白阳性细胞主要是星形胶质细胞,这是以前研究的物种中小鼠所特有的观察结果。蛋白质印迹分析显示,Hp大脑中存在的Tf是外源性的(来自补充注射)。据推测,Tf转运在Hp少突胶质细胞中发现的铁。这些数据表明,尽管减少内源性Hp脑Tf,铁和血浆Tf迁移或运输到适当的细胞(少突胶质细胞),使问题的内源性脑Tf在细胞外铁转运的作用。(C)1995年Wiley-Liss,Inc.
Hypotransferrinemic (Hp) mice have a point mutation or small deletion in the transferrin (Tf) gene, resulting in defective splicing of precursor Tf mRNA. Hp animals produce < 1% of normal Tf levels and require supplemental serum or purified Tf for survival. Because of the lack of endogenous brain Tf, we examined regional and cellular distributions of iron and iron regulatory proteins (Tf and ferritin) in selected brain regions of Hp mice. The regional distribution of iron, Tf, and ferritin in Hp brain was similar to normal except for the pattern of iron staining in hippocampus. The cellular distribution of iron, ferritin, and Tf was similar between Hp and normal animals. The predominant cell type staining for Tf and iron was oligodendrocytes. Qualitative observations suggest that the number of cells staining for iron was similar between Hp and normal mice, whereas the number of Hp Tf-positive cells was reduced. Ferritin immunostaining was similar in both cases. However, ferritin-positive cells were predominantly astrocytes, an observation unique to mice among species studied previously. Western blot analysis revealed that Tf present in Hp brain was of exogenous origin (from supplemental injections). Presumably, Tf transports the iron found in Hp oligodendrocytes. These data demonstrate that, despite reduced endogenous Hp brain Tf, iron and plasma Tf migrate or are transported to the appropriate cells (oligodendrocytes), bringing into question the role of endogenous brain Tf in extracellular iron transport. (C) 1995 Wiley-Liss, Inc.