Defects in regulation of apoptosis in caspase-2-deficient mice

L Bergeron, GI Perez, G Macdonald, L Shi… - Genes & …, 1998 - genesdev.cshlp.org
L Bergeron, GI Perez, G Macdonald, L Shi, Y Sun, A Jurisicova, S Varmuza, KE Latham
Genes & development, 1998genesdev.cshlp.org
During embryonic development, a large number of cells die naturally to shape the new
organism. Members of the caspase family of proteases are essential intracellular death
effectors. Herein, we generated caspase-2-deficient mice to evaluate the requirement for this
enzyme in various paradigms of apoptosis. Excess numbers of germ cells were endowed in
ovaries of mutant mice and the oocytes were found to be resistant to cell death following
exposure to chemotherapeutic drugs. Apoptosis mediated by granzyme B and perforin was …
During embryonic development, a large number of cells die naturally to shape the new organism. Members of the caspase family of proteases are essential intracellular death effectors. Herein, we generated caspase-2-deficient mice to evaluate the requirement for this enzyme in various paradigms of apoptosis. Excess numbers of germ cells were endowed in ovaries of mutant mice and the oocytes were found to be resistant to cell death following exposure to chemotherapeutic drugs. Apoptosis mediated by granzyme B and perforin was defective in caspase-2-deficient B lymphoblasts. In contrast, cell death of motor neurons during development was accelerated in caspase-2-deficient mice. In addition, caspase-2-deficient sympathetic neurons underwent apoptosis more effectively than wild-type neurons when deprived of NGF. Thus, caspase-2 acts both as a positive and negative cell death effector, depending upon cell lineage and stage of development.
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