title: Replacement of K-Ras with H-Ras supports normal embryonic development despite inducing cardiovascular pathology in adult mice.
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.
authors.affiliation: Stazione Zoologica A Dohrn, Laboratory of Animal Genetics, Villa Comunale, 1, 80121 Napoli, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Potenza
authors.forename: Carmine
authors.initials: C
authors.lastname: Vecchione
authors.forename: Antonella
authors.initials: A
authors.lastname: Notte
authors.forename: Assunta
authors.initials: A
authors.lastname: De Rienzo
authors.forename: Annamaria
authors.initials: A
authors.lastname: Rosica
authors.forename: Lisa
authors.initials: L
authors.lastname: Bauer
authors.forename: Andrea
authors.initials: A
authors.lastname: Affuso
authors.forename: Mario
authors.initials: M
authors.lastname: De Felice
authors.forename: Tommaso
authors.initials: T
authors.lastname: Russo
authors.forename: Roberta
authors.initials: R
authors.lastname: Poulet
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cifelli
authors.forename: Gabriella
authors.initials: G
authors.lastname: De Vita
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lembo
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Lauro
mesh_terms: 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