Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair.
bcl-2-/-mice complete embryonic development, but display growth retardation and early mortality postnatally. Hematopoiesis including lymphocyte differentiation is initially normal, but thymus and spleen undergo massive apoptotic involution. Thymocytes require an apoptotic signal to manifest accelerated cell death. Renal failure results from severe polycystic kidney disease characterized by dilated proximal and distal tubular segments and hyperproliferation of epithelium and interstitium. bcl-2-/-mice turn gray with the second hair follicle cycle, implicating a defect in redox-regulated melanin synthesis. The abnormalities in these loss of function mice argue that Bcl-2 is a death repressor molecule functioning in an antioxidant pathway.
Veis
D J
DJ
Department of Medicine, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110.
Sorenson
C M
CM
Shutter
J R
JR
Korsmeyer
S J
SJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D006197:Hair / Q000473:pathology*; D006410:Hematopoiesis; D017496:Hypopigmentation / Q000235:genetics*; D008214:Lymphocytes / Q000502:physiology; D008221:Lymphoid Tissue / Q000196:embryology / Q000473:pathology*; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D007690:Polycystic Kidney Diseases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D013154:Spleen / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D003907:Dexamethasone