Mouse models of cell death.
Cell death is critical for the development and orderly maintenance of cellular homeostasis in metazoans. Developmental genetics in model systems, including Caenorhabditis elegans and Drosophila melanogaster, have helped to identify and order the components of cell-death pathways. An even more complex network of apoptotic pathways has evolved in higher organisms that possess homologs within each set of cell-death regulators. Whereas biochemical studies provide details of molecular mechanisms, genetic models reveal the essential physiologic roles. Transgenic and gene-ablated mice have helped to elucidate mammalian apoptotic pathways and identify the principal effect of each cell death regulator. Here, we review the details of the apoptotic machinery as revealed by mice deficient in critical components of cell-death pathways; we concentrate on cell-death regulators classified as members of the caspase and Bcl2 families or, broadly, as adaptors and mitochondrial released factors.
Ranger
A M
AM
Howard Hughes Medical Institute, Department of Pathology and Medicine, Harvard Medical School, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Malynn
B A
BA
Korsmeyer
S J
SJ
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D053477:Apoptotic Protease-Activating Factor 1; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D053219:Receptors, Tumor Necrosis Factor, Member 25; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction; D051020:bcl-X Protein; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; C494812:Bcl2l1 protein, mouse; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; D047888:Receptors, Tumor Necrosis Factor, Type I; C506034:Tnfrsf25 protein, mouse; D051020:bcl-X Protein; D019014:fas Receptor; D020169:Caspases