K-ras is an essential gene in the mouse with partial functional overlap with N-ras

Leisa Johnson, Doron Greenbaum, Karen Cichowski, Kim Mercer, Elizabeth Murphy, Eric Schmitt, Roderick T. Bronson, Heywood Umanoff, Windfried Edelmann, Raju Kucherlapati, Tyler Jacks

Research output: Contribution to journalArticle

403 Scopus citations

Abstract

Mammalian ras genes are thought to be critical in the regulation of cellular proliferation and differentiation and are mutated in ~30% of all human tumors. However, N-ras and H-ras are nonessential for mouse development. To characterize the normal role of K-ras in growth and development, we have mutated it by gene targeting in the mouse. On an inbred genetic background, embryos homozygous for this mutation die between 12 and 14 days of gestation, with fetal liver defects and evidence of anemia. Thus, K-ras is the only member of the ras gene family essential for mouse embryogenesis. We have also investigated the effect of multiple mutations within the ras gene family. Most animals lacking N-ras function and heterozygous for the K-ras mutation exhibit abnormal hematopoietic development and die between days 10 and 12 of embryogenesis. Thus, partial functional overlap appears to occur within the ras gene family, but K-ras provides a unique and essential function.

Original languageEnglish (US)
Pages (from-to)2468-2481
Number of pages14
JournalGenes and Development
Volume11
Issue number19
DOIs
StatePublished - Oct 1 1997

Keywords

  • Embryogenesis
  • Hematopoiesis
  • K-Ras
  • Knockout mouse
  • N-Ras
  • Oncogene

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Johnson, L., Greenbaum, D., Cichowski, K., Mercer, K., Murphy, E., Schmitt, E., Bronson, R. T., Umanoff, H., Edelmann, W., Kucherlapati, R., & Jacks, T. (1997). K-ras is an essential gene in the mouse with partial functional overlap with N-ras. Genes and Development, 11(19), 2468-2481. https://doi.org/10.1101/gad.11.19.2468