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

Genes and Development - Tập 8 Số 9 - Trang 1019-1029 - 1994
Camilynn I. Brannan1,2,3,4, Archibald S. Perkins1,2,3,4, Kristine S. Vogel1,2,3,4, Nancy Ratner1,2,3,4, Michael L. Nordlund1,2,3,4, S. W. J. Reid1,2,3,4, Arthur M. Buchberg1,2,3,4, N A Jenkins1,2,3,4, Luis F. Parada1,2,3,4, Neal G. Copeland1,2,3,4
1Jefferson Cancer Institute, Department of Microbiol-ogy and Immunology, Philadelphia, Pennsylvania 19107-5541 USA. Cold Spring Harbor Laboratory
2Mammalian Genetics Laboratory, ABL-Basic Research Program, Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201 USA; ~Department of Pathology,
3University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0521 USA
4Yale University School of Medicine, New Haven, Connecticut 06437 USA; 2Department of Anatomy and Cell Biology,

Tóm tắt

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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Genes and Development

Tập 8 Số 9

1019-1029

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