Combined deficiencies of Src, Fyn, and Yes tyrosine kinases in mutant mice.
Three members of the Src family of tyrosine kinases, src, fyn, and yes, are broadly expressed throughout mouse development. Mutations in the c-src and fyn genes were shown previously to lead to restricted nonoverlapping phenotypes only in a subset of cells in which these kinases are expressed. In this work we show that a mutation in the yes gene does not lead to an overt phenotype. Except for brain, the level or distribution of related kinases is not altered in major tissues. To gain further insight into the possibility that these kinases compensate for each other, animals deficient in multiple src-kinases were generated. Whereas most of the src/fyn or src/yes double mutants die perinatally, a substantial proportion of fyn/yes double mutants are viable but undergo degenerative renal changes leading to diffuse segmental glomerulosclerosis. Taken together, these data are consistent with the hypothesis that, at least in some cells, these kinases are able to compensate for the loss of the other related kinases.
Program in Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
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Stein
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Vogel
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Soriano
D000818:Animals; D001483:Base Sequence; D000081247:CSK Tyrosine-Protein Kinase; D003433:Crosses, Genetic; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D016391:Genes, src; D007668:Kidney / Q000002:abnormalities; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics; D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; D019061:src-Family Kinases
D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; C496639:Yes1 protein, mouse; D019061:src-Family Kinases