Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice

The p42 and p44 mitogen-activated protein kinases (MAPKs), also called Erk2 and Erk1, respectively, have been implicated in proliferation as well as i n differentiation programs. The specific role of the p44 MAPK isoform in th e whole animal was evaluated by generation of p44 MAPK-deficient mice by ho mologous recombination in embryonic stem cells. The p44 MAPK(-/-) mice were viable, fertile, and of normal size. Thus, p44 MAPK is apparently dispensa ble and p42 MAPK (Erk2) may compensate for its Loss. However, in p44 MAPK(- /-) mice, thymocyte maturation beyond the CD4(+)CD8(+) stage was reduced by half, with a similar diminution in the thymocyte subpopulation expressing high Levels of T cell receptor (CD3(high)). In p44 MAPK(-/-) thymocytes, pr oliferation in response to activation with a monoclonal antibody to the T c ell receptor in the presence of phorbol myristate acetate was severely redu ced even though activation of p42 MAPK was more sustained in these cells. T he p44 MAPK apparently has a specific role in thymocyte development.