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 Albert, Robert A. Weinberg, Tyler Jacks

Research output: Contribution to journalArticle

223 Citations (Scopus)

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
StatePublished - Oct 10 1994
Externally publishedYes

Fingerprint

Tumors
Animals
Tissue
Stem cells
Liver
Genes
Intermediate Pituitary Gland
Defects
Mutation
Adrenal Medulla
Tumor Suppressor Genes
Cataract
Cerebellum
Hyperplasia
Retina
Carcinogenesis
Erythrocytes
Pregnancy
Neoplasms

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)

Cite this

Williams, B. O., Schmitt, E. M., Remington, L., Bronson, R. T., Albert, D., Weinberg, R. A., & Jacks, T. (1994). Extensive contribution of Rb-deficient cells to adult chimeric mice with limited histopathological consequences. EMBO Journal, 13(18), 4251-4259.

Extensive contribution of Rb-deficient cells to adult chimeric mice with limited histopathological consequences. / Williams, Bart O.; Schmitt, Earlene M.; Remington, Lee; Bronson, Roderick T.; Albert, Daniel; Weinberg, Robert A.; Jacks, Tyler.

In: EMBO Journal, Vol. 13, No. 18, 10.10.1994, p. 4251-4259.

Research output: Contribution to journalArticle

Williams, BO, Schmitt, EM, Remington, L, Bronson, RT, Albert, D, Weinberg, RA & Jacks, T 1994, 'Extensive contribution of Rb-deficient cells to adult chimeric mice with limited histopathological consequences', EMBO Journal, vol. 13, no. 18, pp. 4251-4259.
Williams BO, Schmitt EM, Remington L, Bronson RT, Albert D, Weinberg RA et al. Extensive contribution of Rb-deficient cells to adult chimeric mice with limited histopathological consequences. EMBO Journal. 1994 Oct 10;13(18):4251-4259.
Williams, Bart O. ; Schmitt, Earlene M. ; Remington, Lee ; Bronson, Roderick T. ; Albert, Daniel ; Weinberg, Robert A. ; Jacks, Tyler. / Extensive contribution of Rb-deficient cells to adult chimeric mice with limited histopathological consequences. In: EMBO Journal. 1994 ; Vol. 13, No. 18. pp. 4251-4259.
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