title: Characterization of mice deficient in the Src family nonreceptor tyrosine kinase Frk/rak.
abstract: Frk/rak belongs to a novel family of Src kinases with epithelial tissue-specific expression. Although developmental expression patterns and functional overexpression in vitro have associated these kinases with growth suppression and differentiation, their physiological functions remain largely unknown. We therefore generated mice carrying a null mutation in iyk, the mouse homolog of Frk/rak. We report here that frk/rak(-/-) mice are viable, show similar growth rates to wild-type animals, and are fertile. Furthermore, a 2-year study of health and survival did not identify differences in the incidence and spectrum of spontaneous tumors or provide evidence of hyperplasias in frk/rak(-/-) epithelial tissues. Histological analysis of organs failed to reveal any morphological changes in epithelial tissues that normally express high levels of Frk/rak. Ultrastructural analysis of intestinal enterocytes did not identify defects in brush border morphology or structural polarization, demonstrating that Frk/rak is dispensable for intestinal cytodifferentiation. Additionally, frk/rak-null mice do not display altered sensitivity to intestinal damage induced by ionizing radiation. cDNA microarray analysis revealed an increase in c-src expression and identified subtle changes in the expression of genes regulated by thyroid hormones. Significant decreases in the circulating levels of T3 but not T4 hormone are consistent with this observation and reminiscent of euthyroid sick syndrome, a stress-associated clinical condition.
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Subhashini
authors.initials: S
authors.lastname: Chandrasekharan
authors.forename: Ting Hu
authors.initials: TH
authors.lastname: Qiu
authors.forename: Nawal
authors.initials: N
authors.lastname: Alkharouf
authors.forename: Kelly
authors.initials: K
authors.lastname: Brantley
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: Edison T
authors.initials: ET
authors.lastname: Liu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004848:Epithelium / Q000648:ultrastructure; D005067:Euthyroid Sick Syndromes / Q000209:etiology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007422:Intestines / Q000528:radiation effects / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D011836:Radiation Tolerance; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D019061:src-Family Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D009363:Neoplasm Proteins; D014284:Triiodothyronine; D011505:Protein-Tyrosine Kinases; C092830:FRK protein, human; C490512:Frk protein, mouse; D019061:src-Family Kinases; D013974:Thyroxine