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Fig. 1: Tp53 mutant X. tropicalis develop hematological malignancy and sarcomas.
a Kaplan–Meier survival analysis on cohorts consisting of two clutches of tp53 homozygous knockout (n = 6; red and n = 7; blue) and one clutch of heterozygous tp53 knockout (n = 14; black) X. tropicalis. Statistical analysis was done using the Prism Mantel–Cox test (ns not significant; **p < 0.01; ***p < 0.001). Chi-Squared values and the Hazard ratios are listed in Supplementary table 2A. b X-ray imaging of a 28-month old tp53+/δ4var2 demonstrating ectopic calcified structures (white arrows). c (Left panels) In the wild-type spleen, CD3+ T-cells form a ring-like structure around the PCNA+ B-cells located in the white pulp. (Right panels) Disruption of a normal CD3+ ring-like structure observed in a tp53δ4var2/δ4var2 animal is indicative of hematological malignancy. d Pie chart summarizing the observed splenic immunostaining for CD3 and PCNA in tp53δ4var1/δ4var2 animals. Staining patterns being either normal or with loss of the typical CD3+ ring structure (CD3) with or without ectopic staining of PCNA (CD3/PCNA) in the red pulp. e Photomicrograph of Natt–Herrick stained blood demonstrating a cluster of leukocytes and a normal nucleated erythrocyte. Inset demonstrates a high-magnification photomicrograph of a lymphoblast. f Flow cytometry analysis reveals an increased number of both CD3+ (left) and CD8+ lymphoblasts (right) in peripheral blood of a tp53δ4var1/δ4var2 animal, when compared with an age-matched control. g Histopathology of the liver reveals diffuse infiltration of T-lymphoblasts, also enriched within the liver capillary (white arrow; top inset) and in between the liver parenchymal cells (black arrow; bottom inset). h Sarcoma in a tp53+/δ4var2 animal observed upon gross examination, with associated histopathology and demonstration of malignant nature by PCNA proliferation staining. White scale bar is 100 µm and black scale bar is 5 µM. |
