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, Giuseppe Lembo, Roberto Di Lauro

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)432-437
Number of pages6
JournalEMBO Reports
Volume6
Issue number5
DOIs
Publication statusPublished - May 2005

Keywords

  • Blood pressure
  • Cardiomyopathy
  • Embryonic development
  • H-ras
  • K-ras

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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  • Cite this

    Potenza, N., Vecchione, C., Notte, A., De Rienzo, A., Rosica, A., Bauer, L., Affuso, A., De Felice, M., Russo, T., Poulet, R., Cifelli, G., De Vita, G., Lembo, G., & Di Lauro, R. (2005). Replacement of K-Ras with H-Ras supports normal embryonic development despite inducing cardiovascular pathology in adult mice. EMBO Reports, 6(5), 432-437. https://doi.org/10.1038/sj.embor.7400397