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Development, Vol 117, Issue 1 13-28, Copyright © 1993 by Company of Biologists

JOURNAL ARTICLES

Mice homozygous for a targeted disruption of the proto-oncogene int-2 have developmental defects in the tail and inner ear

SL Mansour, JM Goddard and MR Capecchi
Howard Hughes Medical Institute, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City 84112.

We derived mice that carry a targeted insertion of a neor gene in the int-2 (Fgf-3) proto-oncogene coding sequences. The mutation was found to be recessive and mice that were homozygous for the insertion did not often survive to adulthood. The mutant mice had defects in the development of the tail and inner ear that could be correlated with disruption of int-2 expression in the posterior primitive streak and hindbrain or otic vesicle. While the tail phenotype was 100% penetrant, we found that the inner ear phenotype had reduced penetrance and variable expressivity. The variable expressivity could not be attributed to variability in the genetic background of the mutant allele or to leaky expression from the mutant allele. Thus, we conclude that even in a uniform genetic background, stochastic variation in the expression of a developmental circuit can result in dramatic differences in phenotypic consequences.


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Home page
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Home page
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Home page
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [PDF]

Home page
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Development, May 15, 2000; 127(10): 2113 - 2123.
[Abstract] [PDF]

Home page
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[Abstract] [Full Text]

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[Abstract] [PDF]

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[Abstract] [PDF]

Home page
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[Abstract] [PDF]

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Development, January 1, 2000; 127(1): 143 - 153.
[Abstract] [PDF]

Home page
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Genes & Dev., July 15, 1999; 13(14): 1834 - 1846.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
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J. Biol. Chem., June 11, 1999; 274(24): 17242 - 17248.
[Abstract] [Full Text] [PDF]

Home page
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Home page
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Home page
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