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

• Published in: Genes & development 1994-05, Vol.8 (9), p.1019-1029
• Main Authors: BRANNAN, C. I, PERKINS, A. S, VOGEL, K. S, RATNER, N, NORDLUND, M. L, REID, S. W, BUCHBERG, A. M, JENKINS, N. A, PARADA, L. F, COPELAND, N. G
• Format: Article
• Language: English
• Subjects: Alleles; Animals; Base Sequence; Biological and medical sciences; Embryonic and Fetal Development; Female; Fetal Heart - abnormalities; Ganglia, Sympathetic - embryology; Gene Targeting; Genes, Neurofibromatosis 1; Heart Defects, Congenital - embryology; Heart Defects, Congenital - genetics; Homozygote; Kidney - embryology; Liver - embryology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mitotic Index; Molecular Sequence Data; Muscle, Skeletal - embryology; Mutation; Neural Crest - embryology; Neurology; Tumors of the nervous system. Phacomatoses
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.8.9.1019

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, 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 NF1 patients can be recapitulated in neurofibromin-deficient mice.