TARGETED DISRUPTION OF THE NEUROFIBROMATOSIS TYPE-1 GENE LEADS TO DEVELOPMENTAL ABNORMALITIES IN HEART AND VARIOUS NEURAL CREST-DERIVED TISSUES
TARGETED DISRUPTION OF THE NEUROFIBROMATOSIS TYPE-1 GENE LEADS TO DEVELOPMENTAL ABNORMALITIES IN HEART AND VARIOUS NEURAL CREST-DERIVED TISSUES
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DOI：
10.1101/gad.8.9.1019
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发表时间：
1994-05-01
影响因子：
10.5
通讯作者：
COPELAND, NG
中科院分区：
文献类型：
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作者：
BRANNAN, CI;PERKINS, AS;COPELAND, NG
神经纤维瘤病（NF1）基因与哺乳动物GAP基因具有很高的同源性，是ras信号转导通路的重要调控因子。为了研究NF 1在正常发育中的功能并尝试开发NF 1疾病的小鼠模型，我们在ES细胞中使用基因靶向来产生在小鼠Nf 1基因座上携带无效突变的小鼠。尽管杂合子突变小鼠，年龄达10个月，没有表现出任何明显的异常，纯合子突变胚胎在子宫内死亡。胚胎死亡可能是由于心脏严重畸形。有趣的是，突变胚胎也显示神经嵴衍生的交感神经节增生。这些结果确定了NF1在发育中的新作用，并表明在NE1患者中观察到的一些异常生长现象可以在神经纤维蛋白缺陷小鼠中重现。
The neurofibromatosis (NF1) gene shows significant homology to mammalian GAP and is an important regulator of the ras signal transduction pathway. To study the function of NF1 in normal development and to try and develop a mouse model of NF1 disease, we have used gene targeting in ES cells to generate mice carrying a null mutation at the mouse Nf1 locus. Although heterozygous mutant mice, aged up to 10 months, have not exhibited any obvious abnormalities, homozygous mutant embryos die in utero. Embryonic death is likely attributable to a severe malformation of the heart. Interestingly, mutant embryos also display hyperplasia of neural crest-derived sympathetic ganglia. These results identify new roles for NF1 in development and indicate that some of the abnormal growth phenomena observed in NE1 patients can be recapitulated in neurofibromin-deficient mice.