Post-natal lethality and neurological and gastrointestinal defects in mice with targeted disruption of the A-Raf protein kinase gene

Curr Biol. 1996 May 1;6(5):614-7. doi: 10.1016/s0960-9822(02)00548-1.

Abstract

The Ras/Raf/MEK/MAP kinase cascade transmits signals from activated cell-surface receptors to transcription factors in the nucleus and is an essential component of metazoan intracellular signaling pathways (see, for example, [1-6]). In the mouse, the Raf protein kinase family is comprised of three homologous genes, Raf-1, A-Raf and B-Raf [5] which are ubiquitously expressed in the developing embryo [7]. We have introduced into the mouse germ line a loss-of-function mutation in the X-chromosomal A-Raf gene, by homologous recombination in embryonic stem cells. On a predominantly C57 Bl/6 genetic background, A-Raf-deficient mice displayed neurological and intestinal abnormalities and died between 7 and 21 days post-partum. When the mutated allele was maintained on a predominantly 129/OLA background, by contrast, A-Raf-deficient animals survived to adulthood, did not display obvious intestinal abnormalities, were fertile, but did have a subset of the neurological defects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Digestive System / physiopathology
  • Digestive System Abnormalities*
  • Female
  • Genes, Lethal*
  • Germ-Line Mutation
  • Heterozygote
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nervous System / physiopathology*
  • Protein-Serine-Threonine Kinases / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-raf
  • Recombination, Genetic
  • X Chromosome

Substances

  • Proto-Oncogene Proteins
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf