RESUMO
The pocket proteins pRB, p107 and p130 have established roles in regulating the cell cycle through the control of E2F activity. The pocket proteins regulate differentiation of a number of tissues in both cell cycle-dependent and -independent manners. Prior studies showed that mutation of p107 and p130 in the mouse leads to defects in cartilage development during endochondral ossification, the process by which long bones form. Despite evidence of a role for pRB in osteoblast differentiation, it is unknown whether it functions during cartilage development. Here, we show that mutation of Rb in the early mesenchyme of p107-mutant mice results in severe cartilage defects in the growth plates of long bones. This is attributable to inappropriate chondrocyte proliferation that persists after birth and leads to the formation of enchondromas in the growth plates as early as 8 weeks of age. Genetic crosses show that development of these tumorigenic lesions is E2f3 dependent. These results reveal an overlapping role for pRB and p107 in cartilage development, endochondral ossification and enchondroma formation that reflects their coordination of cell-cycle exit at appropriate developmental stages.
Assuntos
Condrogênese/fisiologia , Condroma/genética , Lâmina de Crescimento/crescimento & desenvolvimento , Proteína do Retinoblastoma/fisiologia , Proteína p107 Retinoblastoma-Like/fisiologia , Animais , Condrogênese/genética , Condroma/patologia , Camundongos , Camundongos Knockout , Mutação , Reação em Cadeia da Polimerase em Tempo Real , Proteína do Retinoblastoma/genética , Proteína p107 Retinoblastoma-Like/genética , Tomografia Computadorizada por Raios XRESUMO
We present here a familial case of a paracentric inversion in man with a short review of the literature. A paracentric inversion of chromosome 10(q11q26) was found in the amniocytes drawn for advanced maternal age. The presence of the inversion was investigated in 35 family members in three generations. No recombinants were recognized. The significance of these data for appropriate genetic counselling and possible reproductive risks is discussed.