Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues.

摘要: The neurofibromatosis (NF1) gene shows significant homology to mammalian GAP and is an important regulator of the ras signal transduction pathway. To study function NF1 in normal development try develop a mouse model disease, we have used targeting ES cells generate mice carrying null mutation at Nf1 locus. Although heterozygous mutant mice, aged up 10 months, not exhibited any obvious abnormalities, homozygous embryos die utero. Embryonic death likely attributable severe malformation heart. Interestingly, also display hyperplasia neural crest-derived sympathetic ganglia. These results identify new roles for indicate that some abnormal growth phenomena observed patients can be recapitulated neurofibromin-deficient