1) Ewing's Sarcoma. Within the preceding year we have shown that zebrafish with EWS/FLI1 leads to mitotic defects with abnormal or multipolar mitotic spindles starting from the bud stage (10hpf). The abnormalities in mitotic spindles were followed by p53-mediated apoptosis in the developing central nervous system (CNS) leading to a reduction in the number of proneural cells, disorganization of neuronal networks, and embryonic lethality by 5 days post-fertilization. 2) Ovarian cancer. We have iidentified zebrafish harboring mutations in the zebrafish BRCA-2 gene. Zebrafish with homozygous mutation of brca2 fail to develop ovaries. However, they develop gonadal tumors over time, a process enhanced with loss of p53.
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