Targeted disruption of int-2 (fgf-3) causes developmental defects in the tail and inner ear.
The int-2 gene (also designated fgf-3) was originally identified because its transcription is activated by the nearby integration of mouse mammary tumor virus in virus-induced tumors. Molecular analyses have revealed that the int-2 gene produces at least four mRNAs, all of which encode a protein that has 40-50% amino acid sequence similarity with the fibroblast growth factors (FGFs). Int-2 gene expression is localized to a small number of discrete sites in the developing mouse, but has not been detected in any nonneoplastic adult tissue. The expression data and the amino acid sequence similarity with the FGFs suggested several potential roles for int-2 during normal development. To evaluate these possibilities, we initiated a genetic analysis of int-2. A gene-targeting protocol was used to generate embryonic stem (ES) cells that are heterozygous for an insertion of the neo(r) gene into the first protein-coding exon of int-2. These cells were used to establish a line of mice that carry the gene disruption. Animals that are heterozygous for the int-2neo allele are normal and fertile. Homozygous mutants survive embryonic development and can be visually identified after 12.5 days of gestation by a short, initially dorsally curled tail. This defect is potentially due to the disruption of int-2 expression in the primitive streak/tail bud. Most of the homozygous mutants die at or soon after birth, but several have survived to adulthood. In addition to the tail phenotype, the surviving homozygotes show, to varying extents, symptoms characteristic of inner ear abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
Mansour
S L
SL
Department of Human Genetics. Eccles Institute of Genetics, University of Utah, Salt Lake City.
D000483:Alleles; D017398:Alternative Splicing; D000818:Animals; D007758:Ear, Inner / Q000002:abnormalities*; D005314:Embryonic and Fetal Development; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000235:genetics*; D006720:Homozygote; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D013623:Tail / Q000002:abnormalities*
C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D011505:Protein-Tyrosine Kinases