PMC

A, B. Kaplan-Meier curves of overall (A) and tumor-free survival (B) of p73−/−, p53+/−p73+/− and p53−/−p73−/− mice. The number of mice of each genotype is indicated. C. Kaplan-Meier curves of tumor-free survival of p53−/−, p53−/−p73+/− and p53−/−p73−/− mice. D. Tumor spectra in mice of the indicated genotypes.

A. The dynamics of T cell lymphoma development in mice of the indicated genotypes. B. LOH analysis at the p73 locus by genomic PCR of tumor tissues derived from p53−/−, p53+/−p73−/−, and p53−/−p73−/− (DKO) mice. Tumor numbers are indicated.

A–C. Quantitative RT-PCR analysis of genes encoding critical factors of T cell development in DN and DP thymocytes of the indicated genotypes. Each sample was analyzed in duplicate. mRNA expression levels were normalized to hypoxanthine-guanine phosphoribosyl transferase (HPRT) mRNA amount.

Hematoxylin and eosin staining of tissues from tumor-bearing p53−/−p73−/− mice showing lymphatic accumulation in lungs (A, B), liver (D), kidney (E), and heart (F). Lung section of a lymphoma-bearing p53−/− mouse is shown for comparison (C). Magnification 4X. The table lists the numbers of thymic lymphomas from mice with the indicated genotypes that either exhibited or lacked clear indications of invasion of peripheral organs by lymphoma.

A, B. Genomyc PCR analysis of internal deletion at the Bcl11b and Notch1 loci in thymocytes from WT, p53−/−, p73−/−, and DKO mice (A), and in lymphomas derived from p53−/−, p53−/−p73+/− and p53−/−p73−/− mice (B). Consistent data were obtained from three mice of each genotype. TCRβ and TCRγ gene rearrangements are shown for controls. Tumor numbers are indicated. C. Relative frequency of rearranged Bcl11b gene in thymocytes from WT, p53−/−, p73−/−, and DKO mice. The results are representative of six mice of each genotype. The error bars represent the standard error.

A. Semi-quantitative RT-PCR analysis of p73 mRNA levels in sorted bone marrow Lin-Sca1+c-Kit+ (LSK) cells, thymic CD4/CD8 double negative (DN), CD4/CD8 double positive (DP), CD4-SP and CD8-SP cells from WT mice. HPRT is a control for equal input. p73−/− thymocytes are shown for control. B. The frequency of LSK lymphoid progenitors in bone marrow and early T lineage progenitors (ETP) in thymi of mice of the indicated genotypes. ETP cells represent a c-Kit-positive subset of the DN1 (CD44+CD25-) population. The error bars represent the standard error obtained from six experiments. C. Relative numbers of DP, CD4-SP and CD8-SP T cell in thymi from 4-week old mice of the indicated genotypes. The error bars represent the standard error. D. Total cell numbers in thymi and spleens of 4 week-old mice of the indicated genotypes. The error bars represent the standard error obtained from six experiments. E, F. Thymocytes from 4-week old mice of the indicated genotypes were stained with antibodies to CD4, CD8, CD25 and CD44. Gating on CD4/CD8 double negative cells. Relative numbers of DN1-4 (E) and absolute numbers of DN3/DN4 subsets (F) are indicated. The error bars represent the standard error obtained from eight experiments. P-values for the difference between WT and p73−/− subsets are shown. G. Annexin V staining of DN and DP thymocytes from 4 week-old mice of the indicated genotypes. The error bars represent the standard error obtained from three experiments.