Exons 10-17 of the Trp53bp2 gene are disrupted in this strain, abolishing gene function. These mice may be useful for studying tumor development and treatment.
Charles D Lopez, Oregon Health and Science University
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.
A targeting vector was designed to replace exons 10-17 of the transformation related protein 53 binding protein 2 (Trp53bp2) gene with a loxP-flanked PGK-neo cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6 females generate a colony of ASPP2+/- mice. These mice were then backcrossed to C57BL/6J mice and then to BALB/cJ for at least 8 generations. Upon arrival at The Jackson Laboratory, mice were bred to BALB/cJ (Stock No. 000651) for at least one generation.
|Allele Name||targeted mutation 1, Charles D Lopez|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Trp53bp2, transformation related protein 53 binding protein 2|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||Exons 10 - 17 were replaced with a floxed neo cassette via homologous recombination. Western blot analysis indicates about a 2-fold reduction in protein expression in MEFs, thymus and liver from heterozygous mice.|
|Mutations Made By|| |
Charles Lopez, Oregon Health and Science University
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or to BALB/cJ inbred mice (Stock No. 000651). Homozygotes exhibit embryonic lethality by day E6.5.