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.

Replacement of K-Ras with H-Ras supports normal embryonic development despite inducing cardiovascular pathology in adult mice / Potenza, N.; Vecchione, C.; Notte, A.; DE RIENZO, A.; Rosica, A.; Bauer, L.; Affuso, A.; DE FELICE, Mario; Russo, Tommaso; Poulet, R.; Cifelli, G.; DE VITA, Gabriella; Lembo, G.; DI LAURO, Roberto. - In: EMBO REPORTS. - ISSN 1469-221X. - STAMPA. - 6:(2005), pp. 432-437.

Replacement of K-Ras with H-Ras supports normal embryonic development despite inducing cardiovascular pathology in adult mice

DE FELICE, MARIO;RUSSO, TOMMASO;DE VITA, GABRIELLA;DI LAURO, ROBERTO
2005

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.
2005
Replacement of K-Ras with H-Ras supports normal embryonic development despite inducing cardiovascular pathology in adult mice / Potenza, N.; Vecchione, C.; Notte, A.; DE RIENZO, A.; Rosica, A.; Bauer, L.; Affuso, A.; DE FELICE, Mario; Russo, Tommaso; Poulet, R.; Cifelli, G.; DE VITA, Gabriella; Lembo, G.; DI LAURO, Roberto. - In: EMBO REPORTS. - ISSN 1469-221X. - STAMPA. - 6:(2005), pp. 432-437.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/202187
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