title: Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues.
abstract: 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.
authors.affiliation: Mammalian Genetics Laboratory, Frederick Cancer Research and Development Center, Maryland 21702-1201.
authors.forename: C I
authors.initials: CI
authors.lastname: Brannan
authors.forename: A S
authors.initials: AS
authors.lastname: Perkins
authors.forename: K S
authors.initials: KS
authors.lastname: Vogel
authors.forename: N
authors.initials: N
authors.lastname: Ratner
authors.forename: M L
authors.initials: ML
authors.lastname: Nordlund
authors.forename: S W
authors.initials: SW
authors.lastname: Reid
authors.forename: A M
authors.initials: AM
authors.lastname: Buchberg
authors.forename: N A
authors.initials: NA
authors.lastname: Jenkins
authors.forename: L F
authors.initials: LF
authors.lastname: Parada
authors.forename: N G
authors.initials: NG
authors.lastname: Copeland
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D005314:Embryonic and Fetal Development; D005260:Female; D005318:Fetal Heart / Q000002:abnormalities*; D005728:Ganglia, Sympathetic / Q000196:embryology*; D018390:Gene Targeting; D016514:Genes, Neurofibromatosis 1; D006330:Heart Defects, Congenital / Q000196:embryology* / Q000235:genetics; D006720:Homozygote; D007668:Kidney / Q000196:embryology; D008099:Liver / Q000196:embryology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008940:Mitotic Index; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000196:embryology; D009154:Mutation; D009432:Neural Crest / Q000196:embryology