MICE WITH REDUCED LEVELS OF P53 PROTEIN EXHIBIT THE TESTICULAR GIANT-CELL DEGENERATIVE SYNDROME

Transgenic mice which carry hybrid p53 promoter-chloramphenicol acetyl transferase (CAT) transgenes were found to ''press CAT enzymatic activ ity predominantly in the testes. Endogenous levels of p53 mRNA and pro tein were lower than in the nontransgenic control mice. The various p5 3 promoter-CAT transgenic mice exhibited in their testes multinucleate d giant cells, a degenerative syndrome resulting presumably from the i nability of the tetraploid primary spermatocytes to complete meiotic d ivision. The giant-cell degenerative syndrome was also observed in som e genetic strains of homozygous p53 null mice. In view of the hypothes is that p53 plays a role in DNA repair mechanisms, it is tempting to s peculate that the physiological function of p53 that is specifically e xpressed in the meiotic pachytene phase of spermatogenesis is to allow adequate time for the DNA reshuffling and repair events which occur a t this phase to be properly completed. Primary spermatocytes which hav e reduced p53 levels are probably impaired with respect to DNA repair, thus leading to the development of genetically defective giant cells that do not mature.