While K-ras is essential for mouse development, expression of the K-ras 4A splice variant is dispensable

Sarah J Plowman, D James Williamson, Maureen J O'Sullivan, Jennifer Doig, Ann-Marie Ritchie, David J Harrison, David W Melton, Mark J Arends, Martin L Hooper, Charles E Patek

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In mammals, the three classical ras genes encode four highly homologous proteins, N-Ras, H-Ras, and the isoforms K-Ras 4A and 4B. Previous studies have shown that K-ras is essential for mouse development and that while K-ras 4A and 4B are expressed during development, K-ras 4A expression is regulated temporally and spatially and occurs in adult kidney, intestine, stomach, and liver. In the present study, the pattern of K-ras 4A expression was examined in a wide range of wild-type adult mouse tissues, and gene targeting was used to generate K-ras 4A-deficient mice to examine its role in development. It was found that K-ras 4A is also expressed in uterus, lung, pancreas, salivary glands, seminal vesicles, bone marrow cells, and cecum, where it was the major K-Ras isoform expressed. Mating between K-ras(tmDelta4A/+) mice produced viable K-ras(tmDelta4A/tmDelta4A) offspring with the expected Mendelian ratios of inheritance, and these mice expressed the K-ras 4B splice variant only. K-ras(tmDelta4A/tmDelta4A) mice were fertile and showed no histopathological abnormalities on inbred (129/Ola) or crossbred (129/Ola x C57BL/6) genetic backgrounds. The results demonstrate that K-Ras 4A, like H- and N-Ras, is dispensable for normal mouse development, at least in the presence of functional K-Ras 4B.
Original languageEnglish
Pages (from-to)9245-9250
Number of pages6
JournalMolecular and Cellular Biology
Issue number24
Publication statusPublished - Dec 2003


  • Alternative splicing
  • Animals
  • Base sequence
  • DNA
  • Female
  • Fertility
  • Gene expression regulation, Developmental
  • Genes, Ras
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, knockout
  • Phenotype
  • Protein Isoforms
  • Tissue distribution


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