查看文章

The cyclin-dependent kinase inhibitor p16^INK4a can induce senescence of human cells, and its loss by deletion, mutation or epigenetic silencing is among the most frequently observed molecular lesions in human cancer^,. Overlapping reading frames in the INK4A/ARF gene encode p16^INK4a and a distinct tumour-suppressor protein, p19^ARF (ref. ). Here we describe the generation and characterization of a p16^Ink4a-specific knockout mouse that retains normal p19^Arf function. Mice lacking p16^Ink4a were born with the expected mendelian distribution and exhibited normal development except for thymic hyperplasia. T cells deficient in p16^Ink4a exhibited enhanced mitogenic responsiveness, consistent with the established role of p16^Ink4a in constraining cellular proliferation. In contrast to mouse embryo fibroblasts (MEFs) deficient in p19^Arf (ref. ), p16^Ink4a-null MEFs possessed normal growth characteristics and …