EXENCEPHALY AND HYDROCEPHALY IN MICE WITH TARGETED MODIFICATION OF THE APOLIPOPROTEIN-B (APO-B) GENE
EXENCEPHALY AND HYDROCEPHALY IN MICE WITH TARGETED MODIFICATION OF THE APOLIPOPROTEIN-B (APO-B) GENE
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DOI：
10.1002/tera.1420510102
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发表时间：
1995-01-01
期刊：
影响因子：
--
通讯作者：
SULIK, KK
中科院分区：
文献类型：
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作者：
HOMANICS, GE;MAEDA, N;SULIK, KK
载脂蛋白B（apoB）是几种脂蛋白的关键结构组分。这些脂蛋白在循环中转运胆固醇、脂质和维生素E。产生截短型apoB的人血浆中apoB、β-脂蛋白、胆固醇和维生素E的浓度较低。这种情况已经通过apoB基因的靶向修饰在小鼠中建模。纯合子转基因小鼠显示出人类疾病的所有特征。出乎意料的是，大约30%的围产期纯合子是露脑的，而那些有封闭的神经管，大约30%是脑积水。后一种情况也在相对较小比例的杂合子小鼠中观察到。妊娠第9天（GD 9）纯合子后代的活体染色显示了一种显著的过度细胞死亡模式，涉及后脑的背板。组织学和扫描电子显微镜分析证实了这一发现。我们推测，正如在GD 9和10胚胎中观察到的那样，不同程度的影响会导致足月胎儿出现一系列畸形，包括脑积水。对维生素E缺乏作为一个可能的致病因素的分析表明，纯合子胎儿确实表现出这种缺乏。已经探索了通过在母体饮食中补充α-生育酚来改善检测。进一步分析这种转基因突变体的承诺，提供重要的信息，相对于缺乏维生素E和其他载脂蛋白B依赖性化合物在畸形的作用。(C)1995 Wiley-Liss，Inc.
Apolipoprotein B (apoB) is a key structural component of several lipoproteins. These lipoproteins transport cholesterol, lipids, and vitamin E in the circulation. Humans that produce truncated forms of apoB have low plasma concentrations of apoB, beta-lipoproteins, cholesterol, and often vitamin E. This condition has been modeled in mice by targeted modification of the apoB gene. Homozygous transgenic mice display all of the hallmarks of the human disorder. Unexpectedly, approximately 30% of the perinatal homozygotes are exencephalic and of those that have closed neural tubes, approximately 30% are hydrocephalic. The latter condition has also been noted in a relatively small proportion of the heterozygous mice. Vital staining of gestational day 9 (GD9) homozygous offspring has illustrated a striking pattern of excessive cell death involving the alar plate of the hindbrain. Histological and scanning electron microscopic analyses have confirmed this finding. We speculate that varying degrees of affect, as noted among GD 9 and 10 embryos, lead to the spectrum of malformations, including hydrocephaly, present in term fetuses. Analysis of vitamin E deficiency as a possible causative factor has illustrated that homozygous fetuses, indeed, show this deficiency. Amelioration of the detects through alpha-tocopherol supplementation of the maternal diet has been explored. Further analyses of this transgenic mutant promise to provide significant information relative to the role of deficiency of vitamin E and other apoB dependent compounds in dysmorphogenesis. (C) 1995 Wiley-Liss, Inc.