Transgenes encoding both type I and type IV c-abl proteins rescue the lethality of c-abl mutant mice.
Mice carrying homozygous mutations in the c-abl gene (abl-(m1) or abl2) exhibit severe, though variable phenotypes, including a high rate of postnatal mortality, runting, morphological abnormalities, a susceptibility to infections, and selected immune system defects. To further determine the role of the c-Abl protein in vivo, we have generated three lines of mice expressing c-abl transgenes. These minigenes encode the two major forms of the c-abl gene product (c-Abl types I and IV) and a kinase defective type IV c-Abl. The transgenic lines, in Abl-positive genetic backgrounds, were phenotypically almost indistinguishable from their non-transgene littermates and expressed the c-abl transgene in a variety of tissues at levels comparable to that of the endogenous c-abl gene. When the transgenes were introduced into a mutant c-abl strain by mating, the mutant c-abl phenotype was almost completely rescued by either of the c-abl type I or type IV transgenes, but not by the kinase-defective transgene. These findings suggest that either of the two alternatively spliced c-abl gene products can provide the in vivo functions of c-Abl, and that these functions are dependent on kinase activity.
Hardin
J D
JD
Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Boast
S
S
Mendelsohn
M
M
de los Santos
K
K
Goff
S P
SP
D000818:Animals; D001483:Base Sequence; D005804:Genes, Lethal; D005816:Genetic Complementation Test; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016315:Proto-Oncogene Proteins c-abl / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*
D016315:Proto-Oncogene Proteins c-abl