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.

journal_name

Mol Cell Biol

authors

Chandrasekharan S,Qiu TH,Alkharouf N,Brantley K,Mitchell JB,Liu ET

doi

10.1128/mcb.22.14.5235-5247.2002

subject

Has Abstract

pub_date

2002-07-01 00:00:00

pages

5235-47

issue

14

eissn

0270-7306

issn

1098-5549

journal_volume

22

pub_type

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