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The Retinoblastoma Gene Regulates Somatic Growth during Mouse Development¹

Department of Molecular Medicine/Institute of Biotechnology, The University of Texas Health Science Center, San Antonio, Texas 78245-3207

Overexpression of the retinoblastoma gene (Rb) in mice leads to the dwarf phenotype. To explore the potential mechanism of Rb effects on the somatic growth, bitransgenic mice with tetracycline-regulated Rb expression were generated, and their phenotypes were compared with those of previously established Rb mouse models. By gestational day 12.5, embryos lacking Rb and those expressing twice the regular amount of Rb are 15% larger and 10–30% smaller, respectively, compared with their wild-type littermates. The dwarf phenotype is associated with increased plasma levels of insulin-like growth factor-I (IGF-I) but not with growth hormone and glucose concentrations. Down-regulation of the Rb transgene expression results in a reduction of the IGF-I plasma concentrations to normalcy and an increase of somatic growth prenatally and postnatally. Consistent with the in vivo results, cells overexpressing Rb require higher thresholds of IGF-I to stimulate proliferation. Thus, Rb plays an integral role for mouse somatic growth and maintenance during ontogenesis, and IGF-I pathway is likely to be a target for such regulation.

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