The retinoblastoma gene regulates somatic growth during mouse development

Overexpression of the retinoblastoma gene (R6) in mice leads to the dwarf p henotype. To explore the potential mechanism of Rb effects on the somatic g rowth, bitransgenic mice with tetracycline-regulated Rb expression were gen erated, and their phenotypes were compared with those of previously establi shed 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% smalle r, respectively, compared with their wild-type littermates. The dwarf pheno type is associated with increased plasma levels of insulin-like growth fact or-I (TGF-I) but not with growth hormone and glucose concentrations. Down-r egulation of the Rb transgene expression results in a reduction of the IGF- I plasma concentrations to normalcy and an increase of somatic growth prena tally and postnatally, Consistent with the in vivo results, cells overexpre ssing Rb require higher thresholds of IGF-I to stimulate proliferation. Thu s, Rb plays an integral role for mouse somatic growth and maintenance durin g ontogenesis, and IGF-I pathway is likely to be a target for such regulati on.