Choorapoikayil, S., Kuiper, R.V., de Bruin, A., and den Hertog, J. (2012) Haploinsufficiency of tumor suppressor pten predisposes to hemangiosarcoma in zebrafish. Disease models & mechanisms. 5(2):241-247.
PTEN is an essential tumor suppressor that antagonizes Akt/PKB signaling. The zebrafish genome encodes two pten genes, ptena and ptenb. Here, we report that zebrafish mutants that retain a single wild type copy of pten, ptena+/-ptenb-/- or ptena-/-ptenb+/-, are viable and fertile. Ptena+/-ptenb-/- fish develop tumors at a relatively high incidence (10.2%) and most tumors developed close to the eye (26/30). Histopathologically,
the tumor masses were associated with the retrobulbar vascular network and diagnosed as hemangiosarcomas. A single tumor was
identified in 42 ptena-/-ptenb+/- fish that was also diagnosed as hemangiosarcoma. Immunohistochemistry indicated that the tumor cells in ptena+/-ptenb-/- and ptena-/-ptenb+/- fish proliferated rapidly and were of endothelial origin. Akt/PKB signaling was activated in the tumors, whereas Ptena was
still detected in tumor tissue from ptena+/-ptenb-/- zebrafish. We conclude that haploinsufficiency of pten predisposes to hemangiosarcoma in zebrafish.