View article

To investigate the function of the Rb-related p107gene, a null mutation in p107 was introduced into the germ line of mice and bred into a BALB/cJ genetic background. Mice lackingp107 were viable and fertile but displayed impaired growth, reaching about 50% of normal weight by 21 days of age. Mutant mice exhibited a diathetic myeloproliferative disorder characterized by ectopic myeloid hyperplasia in the spleen and liver. Embryonicp107−/− fibroblasts and primary myoblasts isolated from adult p107−/− mice displayed a striking twofold acceleration in doubling time. However, cell sort analysis indicated that the fraction of cells in G 1, S, and G 2 was unaltered, suggesting that the different phases of the cell cycle in p107−/− cells was uniformly reduced by a factor of 2. Western analysis of cyclin expression in synchronized p107−/− fibroblasts revealed that expression of cyclins E and A preceded that of D1. Mutant …