PAM14, a Novel MRG- and Rb-Associated Protein, Is Not Required for Development and T-Cell Function in Mice

Abstract

PAM14 has been found to associate in complexes with the MORF4/MRG family of proteins as well as Rb, the tumor suppressor protein. This suggested that it might be involved in cell growth, immortalization, and/or senescence. To elucidate the in vivo function of PAM14, we characterized the expression pattern of mouse Pam14 and generated PAM14-deficient (Pam14^{− / −}) mice. Pam14 was widely expressed in all mouse tissues and as early as 7 days during embryonic development. Despite this ubiquitous expression in wild-type mice, Pam14^{− / −} mice were healthy and fertile. Response to mitogenic stimulation and production of interleukin-2 were the same in stimulated splenic T cells from Pam14^{− / −} mice as in control littermates. Cell growth rates of mouse embryonic fibroblasts (MEFs) from all three genotypes were the same, and immortalized cells were obtained from all cell cultures during continuous culture. There was also no difference in expression of growth-related genes in response to serum stimulation in the null versus control MEFs. These data demonstrate that PAM14 is not essential for normal mouse development and cell cycle control. PAM14 likely acts as an adaptor protein in nucleoprotein complexes and is probably compensated for by another functionally redundant protein(s).

We thank Simona Varani for help with ES cell technology, Lei Chen for injection of ES cells into blastocysts, Florante Quiocho for PAM14 expression plasmid, Nicholas J. Dyson for plasmids containing fragment for probes, Adrian Donias for ELISA, Johanna Echigo for maintaining mice, Meihua Song for purification of antibodies, and James R. Smith for discussion.

This work was supported by grants from the NIA, P01AG2752, and the Ellison Medical Foundation (O.M.P.S.) and NCI CA60651 (M.M.M.).