BCL-2 family member BOK is widely expressed but its loss has only minimal impact in mice

• Published in: Cell death and differentiation 2012-06, Vol.19 (6), p.915-925
• Main Authors: Ke, F, Voss, A, Kerr, J B, O'Reilly, L A, Tai, L, Echeverry, N, Bouillet, P, Strasser, A, Kaufmann, T
• Format: Article
• Language: English
• Subjects: 631/136/334/1874/345; 631/45/612; 631/80/82/23; Animals; Apoptosis; Biochemistry; Biomedical and Life Sciences; Brain research; Cell Biology; Cell Cycle Analysis; Cell death; Deoxyribonucleic acid; DNA; Female; Life Sciences; Medical research; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Myeloid Cells - immunology; Myeloid Cells - metabolism; Original Paper; Ovary - metabolism; Ovary - pathology; Proteins; Proto-Oncogene Proteins c-bcl-2 - deficiency; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; RNA, Messenger - metabolism; Stem Cells; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Uterus - metabolism; Uterus - pathology
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/cdd.2011.210

BOK/MTD was discovered as a protein that binds to the anti-apoptotic Bcl-2 family member MCL-1 and shares extensive amino-acid sequence similarity to BAX and BAK, which are essential for the effector phase of apoptosis. Therefore, and on the basis of its reported expression pattern, BOK is thought to function in a BAX/BAK-like pro-apoptotic manner in female reproductive tissues. In order to determine the function of BOK, we examined its expression in diverse tissues and investigated the consequences of its loss in Bok −/− mice. We confirmed that Bok mRNA is prominently expressed in the ovaries and uterus, but also observed that it is present at readily detectable levels in several other tissues such as the brain and myeloid cells. Bok −/− mice were produced at the expected Mendelian ratio, appeared outwardly normal and proved fertile. Histological examination revealed that major organs in Bok −/− mice displayed no morphological aberrations. Although several human cancers have somatically acquired copy number loss of the Bok gene and BOK is expressed in B lymphoid cells, we found that its deficiency did not accelerate lymphoma development in E μ-Myc transgenic mice. Collectively, these results indicate that Bok may have a role that largely overlaps with that of other members of the Bcl-2 family, or may have a function restricted to specific stress stimuli and/or tissues.