Mice with reduced levels of p53 protein exhibit the testicular giant-cell degenerative syndrome.
Transgenic mice which carry hybrid p53 promoter-chloramphenicol acetyltransferase (CAT) transgenes were found to express CAT enzymatic activity predominantly in the testes. Endogenous levels of p53 mRNA and protein were lower than in the nontransgenic control mice. The various p53 promoter-CAT transgenic mice exhibited in their testes multinucleated giant cells, a degenerative syndrome resulting presumably from the inability of the tetraploid primary spermatocytes to complete meiotic division. The giant-cell degenerative syndrome was also observed in some genetic strains of homozygous p53 null mice. In view of the hypothesis that p53 plays a role in DNA repair mechanisms, it is tempting to speculate that the physiological function of p53 that is specifically expressed in the meiotic pachytene phase of spermatogenesis is to allow adequate time for the DNA reshuffling and repair events which occur at this phase to be properly completed. Primary spermatocytes which have 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.
Rotter
V
V
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Schwartz
D
D
Almon
E
E
Goldfinger
N
N
Kapon
A
A
Meshorer
A
A
Donehower
L A
LA
Levine
A J
AJ
D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D016158:Genes, p53; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D013577:Syndrome; D013737:Testis / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D015500:Chloramphenicol O-Acetyltransferase