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- Title
Replacement of K-Ras with H-Ras supports normal embryonic development despite inducing cardiovascular pathology in adult mice.
- Authors
Potenza, Nicoletta; Vecchione, Carmine; Notte, Antonella; De Rienzo, Assunta; Rosica, Annamaria; Bauer, Lisa; Affuso, Andrea; De Felice, Mario; Russo, Tommaso; Poulet, Roberta; Cifelli, Giuseppe; De Vita, Gabriella; Lembo, Giuseppe; Di Lauro, Roberto
- Abstract
Ras proteins are highly related GTPases that have key roles in regulating growth, differentiation and tumorigenesis. Gene-targeting experiments have shown that, out of the three mammalian ras genes, only K-ras is essential for normal mouse embryogenesis, and that mice deprived of H-ras and/or N-ras show no major phenotype. We generated mice (HrasKI) in which the K-ras gene had been modified to encode H-Ras protein. HrasKI mice produce undetectable amounts of K-Ras but-in contrast to mice homozygous for a null K-ras allele-they are born at the expected mendelian frequency, indicating that H-Ras can be substituted for K-Ras in embryonic development. However, adult HrasKI mice show dilated cardiomyopathy associated with arterial hypertension. Our results show that K-Ras can be replaced by H-Ras in its essential function in embryogenesis, and indicate that K-Ras has a unique role in cardiovascular homeostasis.
- Publication
EMBO reports, 2005, Vol 6, Issue 5, p432
- ISSN
1469-221X
- Publication type
Journal Article
- DOI
10.1038/sj.embor.7400397