The Bax-/-Bak-/- Mouse: a Model for Apoptosis
The bax -/- bak -/- double-deficient mouse has provided a unique tool to study apoptosis. These mice display severe defects in both developmental apoptosis and regulation of tissue homeostasis. Developmental defects include persistent interdigital webs in the adult mouse. A defect in tissue homeostasis is illustrated in the hematopoietic system where lymphocytosis, enlarged lymphoid organs and lymphocytic infiltration in parenchymal organs is seen. In addition, defects in thymocyte development, negative selection and T cell homeostasis is seen. The central nervous system of the bak -/- bak -/- mice show an excess of cells in areas where neural progenitor cells are known to reside. Primary cells as well as cell lines derived from the bax -/- bax -/- mouse display resistance to a multitude of apoptotic stimuli and has helped to provide a model for the regulation of the cell intrinsic apoptotic pathway.
KeywordsNegative Selection Neural Progenitor Cell Apoptotic Stimulus Bone Marrow Chimera Growth Factor Withdrawal
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- Green, D. R. (2000). Apoptotic pathways: paper wraps stone blunts scissors. Cell 102, 1–4.Google Scholar
- Lei, K., Nimnual, A., Zong, W. X., Kennedy, N. J., Flavell, R. A., Thompson, C. B., Bar-Sagi, D., and Davis, R. J. (2002). The Bax subfamily of Bc12-related proteins is essential for apoptotic signal transduction by c-Jun NH(2)-terminal kinase. Mol Cell Bio122, 4929–4942.Google Scholar
- Lindsten, T., Ross, A. J., King, A., Zong, W. X., Rathmell, J. C., Shiels, H. A., Ulrich, E., Waymire, K. G., Mahar, P., Frauwirth, K., et al. (2000). The combined functions of proapoptotic BcI-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell 6, 1389–1399.PubMedCrossRefGoogle Scholar
- McClintock, D. S., Santore, M. T., Lee, V. Y., Brunelle, J., Budinger, G. R., Zong, W. X., Thompson, C. B., Hay, N., and Chandel, N. S. (2002). Bc1–2 family members and functional electron transport chain regulate oxygen deprivation-induced cell death. Mol Cell Biol 22, 94–104.PubMedCrossRefGoogle Scholar
- Motoyama, N., Wang, F., Roth, K. A., Sawa, H., Nakayama, K., Negishi, I., Senju, S., Zhang, Q., Fujii, S., and et al. (1995). Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. Science 267, 1506–1510.Google Scholar
- Puthalakath, H., Villunger, A., O’Reilly, L. A., Beaumont, J. G., Coultas, L., Cheney, R. E., Huang, D. C., and Strasser, A. (2001). Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. Science 293, 1829–1832.PubMedCrossRefGoogle Scholar
- Scaffidi, C., Fulda, S., Srinivasan, A., Friesen, C., Li, F., Tomaselli, K. J., Debatin, K. M., Krammer, P. H., and Peter, M. E. (1998). Two CD95 (APO-l/Fas) signaling pathways. Embo J 17, 1675–1687.Google Scholar
- Shinjyo, T., Kuribara, R., Inukai, T., Hosoi, H., Kinoshita, T., Miyajima, A., Houghton, P. J., Look, A. T., Ozawa, K., and Inaba, T. (2001). Downregulation of Bim, a proapoptotic relative of Bc1–2, is a pivotal step in cytokine-initiated survival signaling in murine hematopoietic progenitors. Mol Cell Bio121, 854–864.Google Scholar
- Wei, M. C., Zong, W. X., Cheng, E. H., Lindsten, T., Panoutsakopoulou, V., Ross, A. J., Roth, K. A., MacGregor, G. R., Thompson, C. B., and Korsmeyer, S. J. (2001). Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292, 727–730.PubMedCrossRefGoogle Scholar