Extensive contribution of Rb-deficient cells to adult chimeric mice with limited histopathological consequences

Bart O. Williams, Earlene M. Schmitt, Lee Remington, Roderick T. Bronson, Daniel M. Albert, Robert A. Weinberg, Tyler Jacks

Research output: Contribution to journalArticle

224 Scopus citations

Abstract

Homozygosity for a mutation in the Rb tumor suppressor gene causes mid-gestation embryonic lethality in the mouse. Using a two-step targeting protocol, we have constructed Rb homozygous mutant mouse embryonic stem cells and used them to create chimeric animals partially composed of Rb-deficient cells. Analysis of these chimeras demonstrates widespread contribution of the mutant cells to adult tissues, including the retina and mature erythrocytes. Despite the presence of large numbers of Rb-deficient cells in most tissues of these mice, they are remarkably normal but do exhibit certain histological defects including cataracts, hyperplasia of the adrenal medulla, and enlarged cells in the cerebellum and the liver. Like animals heterozygous for the Rb mutation, the chimeras develop tumors of the intermediate lobe of the pituitary, and the rate of pituitary tumorigenesis is greatly accelerated.

Original languageEnglish (US)
Pages (from-to)4251-4259
Number of pages9
JournalEMBO Journal
Volume13
Issue number18
DOIs
StatePublished - 1994

Keywords

  • Embryonic lethality
  • Mouse
  • Rb tumor suppressor gene
  • Tumorigenesis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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