Replacement of K-Ras with H-Ras supports normal embryonic development despite inducing cardiovascular pathology in adult mice.
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.
Potenza
Nicoletta
N
Stazione Zoologica A Dohrn, Laboratory of Animal Genetics, Villa Comunale, 1, 80121 Napoli, Italy.
Vecchione
Carmine
C
Notte
Antonella
A
De Rienzo
Assunta
A
Rosica
Annamaria
A
Bauer
Lisa
L
Affuso
Andrea
A
De Felice
Mario
M
Russo
Tommaso
T
Poulet
Roberta
R
Cifelli
Giuseppe
G
De Vita
Gabriella
G
Lembo
Giuseppe
G
Di Lauro
Roberto
R
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000473:pathology; D047108:Embryonic Development / Q000235:genetics* / Q000502:physiology; D011905:Genes, ras / Q000235:genetics* / Q000502:physiology; D006973:Hypertension / Q000235:genetics / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains