| First Author | Abraham KM | Year | 1991 |
| Journal | J Exp Med | Volume | 173 |
| Issue | 6 | Pages | 1421-32 |
| PubMed ID | 1709675 | Mgi Jnum | J:109250 |
| Mgi Id | MGI:3626163 | Doi | 10.1084/jem.173.6.1421 |
| Citation | Abraham KM, et al. (1991) Delayed thymocyte development induced by augmented expression of p56lck. J Exp Med 173(6):1421-32 |
| abstractText | Accumulating evidence supports the contention that CD4 and CD8 receptor molecules play a critical signaling role during thymocyte development. The lymphocyte-specific protein tyrosine kinase (p56lck), by virtue of its physical association with these surface components, provides a likely candidate for the biochemical signal transducing element required for these effects. To investigate the function of p56lck in T lymphocytes, transgenic mice were produced that carry either the wild-type lck gene or a mutated lck gene encoding a constitutively activated form of p56lck (p56lckF505). Both transgenes were expressed in thymocytes under the control of the lck proximal promoter element. A large set of founder animals was obtained in which steady-state accumulation of lck transgene mRNA directly correlated with transgene copy number, suggesting that this transgene contains a dominant control region. Progeny of these founders exhibited a transgene-dependent dose-related decrease in the production of thymocytes bearing functional antigen receptors. This effect was strictly dependent on p56lck activity, in that both wild-type and mutated versions of the genes induced similar effects with differing efficiencies. Remarkably, even a twofold increase in p56lck abundance was sufficient to substantially disrupt the appearance of functional thymocytes. These results indicate that thymocyte maturation is regulated in part by signals derived from p56lck. |
