title: Mice homozygous for a targeted disruption of the proto-oncogene int-2 have developmental defects in the tail and inner ear.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City 84112.
authors.forename: S L
authors.initials: SL
authors.lastname: Mansour
authors.forename: J M
authors.initials: JM
authors.lastname: Goddard
authors.forename: M R
authors.initials: MR
authors.lastname: Capecchi
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D007758:Ear, Inner / Q000002:abnormalities* / Q000473:pathology; D005808:Genes, Recessive / Q000502:physiology*; D006720:Homozygote; D051379:Mice; D008817:Mice, Mutant Strains; D016254:Mutagenesis, Insertional / Q000379:methods; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013623:Tail / Q000002:abnormalities* / Q000473:pathology; D051153:Wnt Proteins; D029961:Zebrafish Proteins
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D011505:Protein-Tyrosine Kinases