A loxP-flanked PGK-neo cassette replaces exons 10-17 of the transformation related protein 53 binding protein 2 (Trp53bp2) gene, abolishing gene function in this strain. ASPP2, encoded by the Trp53bp2 gene, is a pro-apoptotic protein which also inhibits cell growth through interactions with other regulatory molecules including members of the p53 family. The disrupted exons in this mutant include codons for the ankyrin repeat and SH3 domain, required for interaction with p53 family members. Homozygotes exhibit embryonic lethality by embryonic day 6.5. Heterozygous mice are viable, fertile and exhibit increased incidence of spontaneous tumors as they age. γ-irradiated heterozygotes exhibit an increased incidence of high-grade thymic T cell lymphomas and attenuated apoptotic response in primary thymocytes.
