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 / Nicoletta, Potenza; Carmine, Vecchione; Antonella, Notte; Assunta De, Rienzo; Annamaria, Rosica; Lisa, Bauer; Andrea, Affuso; Mario De, Felice; Tommaso, Russo; Roberta, Poulet; Giuseppe, Cifelli; Gabriella De, Vita; Lembo, Giuseppe; Roberto Di, Lauro. - In: EMBO REPORTS. - ISSN 1469-221X. - STAMPA. - 6:5(2005), pp. 432-437. [10.1038/sj.embor.7400397]
Replacement of K-Ras with H-Ras supports normal embryonic development despite inducing cardiovascular pathology in adult mice
LEMBO, Giuseppe;
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.