P53-dependent apoptosis produced by Rb-deficiency in the developing mouse lens

The retinoblastoma tumour-suppressor gene ( has been implicated in negative growth regulation, induction of differentiation, and inhibition of cellular transformation¹. Homozygous inactivation of the gene in the mouse leads to mid-gestational lethality with defects in erythropoiesis and neurogenesis^2-4. Here we describe the effects of the deficient state on the development of the ocular lens. The regional compartmentalization of growth, differentiation and apoptosis in the developing lens provides an ideal system to examine more closely the relationships of these processes We demonstrate that loss of function is associated with unchecked proliferation, impaired expression of differentiation markers, and inappropriate apoptosis in lens fibre cells. In addition, we show that ectopic apoptosis in deficient lenses is dependent on because embryos doubly null for and show a nearly complete suppression of this effect. This developmental system provides a framework for understanding the consequences of the frequent mutation of both and in human cancer.