Expression of a retinoblastoma transgene results in dwarf mice

Yves Jean Bignon, Yumay Chen, Chi Yao Chang, Daniel J. Riley, Jolene J. Windle, Pamela L. Mellon, Wen Hwa Lee

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Introduction of the normal retinoblastoma gene (RB) into different tumor cells possessing inactivated RB genes suppresses their tumorigenicity in nude mice. These results suggest that RB replacement is a potential strategy for developing future clinical treatments of cancer. In a transgenic mouse model, we found that the quantity of RB protein in a given cell may play an important role in dictating its effect. Four founder mice containing 1-7 copies of a human RB cDNA transgene under the transcriptional control of the human RB promoter were generated. Most of the transgenic mice were smaller than nontransgenic littermates. This effect was found as early as embryonic day 15. The degree of dwarfism correlated roughly with the copy number of the transgene and the corresponding level of RB protein. The expression pattern of the transgene products was similar to that of the endogenous mouse RB gene with regard to tissue and temporal distribution. Transferring the transgene to RB deficient mice, which are nonviable, resulted in the development of normal, healthy mice, indicating that the human RB gene can functionally complement the mouse homolog. These studies demonstrate that the effect of RB on overall mouse development is closely dependent upon its dosage.

Original languageEnglish (US)
Pages (from-to)1654-1662
Number of pages9
JournalGenes and Development
Volume7
Issue number9
DOIs
StatePublished - 1993

Keywords

  • Dwarf
  • Growth
  • Retinoblastoma gene
  • Transgenic mice

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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