The Ron STK receptor tyrosine kinase is essential for peri-implantation development in the mouse

被引:75
作者
Muraoka, RS
Sun, WY
Colbert, MC
Waltz, SE
Witte, DP
Degen, JL
Degen, SJF
机构
[1] Childrens Hosp Res Fdn, Div Dev Biol, Cincinnati, OH 45229 USA
[2] Univ Cincinnati, Coll Med, Grad Program Dev Biol, Cincinnati, OH 45229 USA
[3] Childrens Hosp Res Fdn, Div Mol Cardiovasc Biol, Cincinnati, OH 45229 USA
[4] Childrens Hosp Res Fdn, Div Pathol, Cincinnati, OH 45229 USA
关键词
D O I
10.1172/JCI6091
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The Ron/STK receptor tyrosine kinase is a member of the c-Met family of receptors and is activated by hepatocyte growth factor-like protein (HGFL). Ron activation results in a variety of cellular responses in vitro, such as activation of macrophages, proliferation, migration, and invasion, suggesting a broad biologic role in vivo. Nevertheless, HGFL-deficient mice grow to adulthood with few appreciable phenotypic abnormalities. We report here that in striking contrast to the loss of its only known ligand, complete loss of Ron leads to early embryonic death. Embryos that are devoid of Ron (Ron(-/-)) are viable through the blastocyst stage of development but fail to survive past the peri-implantation period. In situ hybridization analysis demonstrates that Ron is expressed in the trophectoderm at embryonic day (E) 3.5 and is maintained in extraembryonic tissue through E7.5, compatible with an essential function at this stage of development. Hemizygous mice (Ron(+/-)) grow to adulthood; however, these mice are highly susceptible to endotoxic shock and appear to be compromised in their ability to downregulate nitric oxide production. These results demonstrate a novel role for Ron in early mouse development and suggest that Ron plays a limiting role in the inflammatory response.
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页码:1277 / 1285
页数:9
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