Use of a murine xenograft model for canine transmissible venereal tumor.

Objective: To develop a murine model for canine transmissible venereal tumor (CTVT).

Animals: Thirty-three 6-week-old NOD/LtSz-scid (NOD/SCID) mice and seven 6-week-old C57BL/6J mice.

Procedure: Samples of CTVT were excised from a 3-year-old dog and inoculated SC into ten 6-week-old NOD/SCID mice to induce growth of xenograft transmissible venereal tumor (XTVT).

p53 tumor suppressor gene expression in the mouse ovary during an artificially induced ovulatory cycle.

Objective: To evaluate the expression of p53 in the mouse ovary during an artificially induced ovulatory cycle.

Study Design: Ovulation induction was performed using pregnant mares' serum gonadotropin/human chorionic gonadotropin (PMSG/hCG). First, a p53 promoter-chloramphenicol acetyl transferase (CAT) transgenic mouse model was used.

Accentuated apoptosis in normally developing p53 knockout mouse embryos following genotoxic stress.

In order to identify the alternative pathways which may substitute for the p53 function during embryogenesis, we have focused our studies on p53 -/- normally developing mouse embryos that survived a genotoxic stress. We assumed that under these conditions p53-independent pathways, which physiologically control genomic stability, are enhanced. We found that while p53 +/+ mouse embryos elicited, as expected, a p53-dependent apoptosis, p53-/- normally developing mice exhibited an accentuated p53-independent apoptotic response.

Does wild-type p53 play a role in normal cell differentiation?

Inactivation of the p53 tumor suppressor gene plays a major role in malignant transformation. The central question in this issue is concerned with the understanding of the function of p53 in normal cells and its deregulation in cancer cells. Several in vitro and in vivo experimental models have indicated that induction of cells to undergo differentiation involve up-regulation in the expression of the p53.

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.

Testicular tissue-specific expression of the p53 suppressor gene.

The hybrid transgene approach was adapted to study the physiological pathway(s) in which the p53 suppressor gene is involved. p53 promoter-CAT transgenic mice were found to express enzymatic CAT activity predominantly in the testes. In situ hybridization indicated that expression of the transgene as well as the endogenous p53 agreed with the typical wave and cycle patterns of spermatogenesis.

Selecting, accelerating and suppressing interactions between macrophages and tumor cells.

Studies were carried out to test whether thioglycollate-induced macrophages (T-PM phi) exert a selective effect on 3LL tumor cells. One million 3LL tumor cells and 10 X 10(6) thioglycollate-elicited peritoneal macrophages were admixed and inoculated subcutaneously in C57BL/6 mice. This procedure was repeated for a series of 6-15 consecutive transplant generations.