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

Camilynn I. Brannan, Archibald S. Perkins, Kristine S. Vogel, Nancy Ratner, Michael L. Nordlund, Susan W. Reid, Arthur M. Buchberg, Nancy A. Jenkins, Luis F. Parada, Neal G. Copeland

Research output: Contribution to journalArticle

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

Original languageEnglish (US)
Pages (from-to)1019-1029
Number of pages11
JournalGenes and Development
Volume8
Issue number9
StatePublished - 1994

Fingerprint

Neurofibromatosis 1 Genes
Neurofibromatosis 1
Congenital Heart Defects
Neural Crest
Embryonic Structures
Neurofibromin 1
Sympathetic Ganglia
Neurofibromatoses
Gene Targeting
Hyperplasia
Signal Transduction
Mutation
Growth
Genes

Keywords

  • ES cells
  • Neurofibromatosis
  • NF1
  • Ras
  • transgenic mice

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Brannan, C. I., Perkins, A. S., Vogel, K. S., Ratner, N., Nordlund, M. L., Reid, S. W., ... Copeland, N. G. (1994). Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues. Genes and Development, 8(9), 1019-1029.

Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues. / Brannan, Camilynn I.; Perkins, Archibald S.; Vogel, Kristine S.; Ratner, Nancy; Nordlund, Michael L.; Reid, Susan W.; Buchberg, Arthur M.; Jenkins, Nancy A.; Parada, Luis F.; Copeland, Neal G.

In: Genes and Development, Vol. 8, No. 9, 1994, p. 1019-1029.

Research output: Contribution to journalArticle

Brannan, CI, Perkins, AS, Vogel, KS, Ratner, N, Nordlund, ML, Reid, SW, Buchberg, AM, Jenkins, NA, Parada, LF & Copeland, NG 1994, 'Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues', Genes and Development, vol. 8, no. 9, pp. 1019-1029.
Brannan, Camilynn I. ; Perkins, Archibald S. ; Vogel, Kristine S. ; Ratner, Nancy ; Nordlund, Michael L. ; Reid, Susan W. ; Buchberg, Arthur M. ; Jenkins, Nancy A. ; Parada, Luis F. ; Copeland, Neal G. / Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues. In: Genes and Development. 1994 ; Vol. 8, No. 9. pp. 1019-1029.
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