title: Diminishing apoptosis by deletion of Bax or overexpression of Bcl-2 does not protect against infectious prion toxicity in vivo.
abstract: B-cell lymphoma protein 2 (Bcl-2) and Bcl-2-associated X protein (Bax), key antiapoptotic and proapoptotic proteins, respectively, have important roles in acute and chronic models of neurologic disease. Several studies have implicated Bax and Bcl-2 in mediating neurotoxicity in prion diseases. To determine whether diminishing apoptotic cell death is protective in an infectious prion disease model we inoculated mice that either were null for proapoptotic Bax or overexpressed antiapoptotic Bcl-2. Interestingly, genetic manipulation of apoptosis did not lessen the clinical severity of disease. Moreover, some disease parameters, such as behavioral alterations and death, occurred slightly earlier in mice that are null for Bax or overexpress Bcl-2. These results suggest that Bax and Bcl-2 mediated apoptotic pathways are not the major contributing factor to the clinical or pathological features of infectious prion disease.
authors.affiliation: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Steele
authors.forename: Oliver D
authors.initials: OD
authors.lastname: King
authors.forename: Walker S
authors.initials: WS
authors.lastname: Jackson
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Hetz
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Borkowski
authors.forename: Peter
authors.initials: P
authors.lastname: Thielen
authors.forename: Robert
authors.initials: R
authors.lastname: Wollmann
authors.forename: Susan
authors.initials: S
authors.lastname: Lindquist
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D017096:Prion Diseases / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D011328:Prions / Q000037:antagonists & inhibitors / Q000633:toxicity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000172:deficiency / Q000235:genetics* / Q000502:physiology
chemical_list: D011328:Prions; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein