PreprintCited by 641Neurofibromatosis and Schwannoma CasesNeuroblastoma Research and TreatmentsDevelopmental Biology and Gene Regulation

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

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Brannan, C I, Perkins, A S, Vogel, K S, Ratner, N, Nordlund, M L, Reid, S W, Buchberg, A M, Jenkins, N A +2 more·1994·Genes & Development

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.

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  1. Cochard, P., M. Goldstein, and I.B. Black. 1978. Ontogenic ap- pearance and disappearance of tyrosine hydroxylase and cat- echolamines in the rat embryo. Proc. Natl. Acad. Sci. 75: 2986-2990.

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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.
Affiliations
Cold Spring Harbor Laboratory (US)
Venue
Genes & Development
Published
1994-05-01
Volume
8
Issue
9
Pages
1019-1029
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2159562139
Cited by
641
References
42
Citations by year
2026: 2 · 2025: 9 · 2024: 17 · 2023: 10 · 2022: 10 · 2021: 19 · 2020: 14 · 2019: 9 · 2018: 16 · 2017: 11 · 2016: 17 · 2015: 14 · 2014: 17 · 2013: 23 · 2012: 33
Type
posted content
Language
en
Open access
Locations
  • Genes & Development (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Health and Human Services
  • James S. McDonnell Foundation
  • National Institutes of Health (n01co074101-034)
  • National Cancer Institute (N01 CO-74101)
  • National Institute of Neurological Disorders and Stroke (NS-28840, R01NS028840)
Topics
  • Health Sciences › Medicine › Neurology › Neurofibromatosis and Schwannoma Cases
  • Health Sciences › Medicine › Neurology › Neuroblastoma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
neurofibromatosis type 1, NF1 gene, neurofibromin, null mutations, cardiac anomalies, neural crest, Ras signaling, developmental abnormalities, mouse model
MeSH terms
Alleles, Animals, Base Sequence, Female, Embryonic and Fetal Development, Fetal Heart, Ganglia, Sympathetic, Heart Defects, Congenital, Homozygote, Kidney, Liver, Male, Mice, Inbred C57BL, Mice, Transgenic, Mitotic Index, Molecular Sequence Data, Mutation, Neural Crest, Genes, Neurofibromatosis 1, Gene Targeting, Muscle, Skeletal, Mice

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