Deficiency of Bax and Bak protects photoreceptors from light damage in vivo.
Photoreceptors of bax(-/-)bak(-/-) but neither bax(-/-) mice nor bak(-/-) mice are protected from developmental apoptosis, suggesting that bax(-/-)bak(-/-) photoreceptors may also be protected from pathologic apoptosis. To test this possibility, we exposed bax(-/-)bak(-/-) and bax(-/-) mice to bright light, which normally induces photoreceptor death. Photoreceptors in bax(-/-)bak(-/-) mice were protected from death compared to bax(-/-) mice as indicated by a reduction in the number of TUNEL-positive photoreceptor nuclei 24 h following light damage and almost complete preservation of photoreceptors 7 days following light damage. These results provide the first in vivo evidence that combined deficiency of Bax and Bak can rescue cells from a pathologic stimulus more effectively than Bax deficiency and suggest that combined deficiency of Bax and Bak may also protect cells from other insults.
FM Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, PA, USA.
P
P
Hahn
T
T
Lindsten
A
A
Lyubarsky
G-S
GS
Ying
E N
EN
Pugh
C B
CB
Thompson
J L
JL
Dunaief
D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004596:Electroretinography; D005123:Eye / Q000473:pathology*; D005131:Eye Injuries / Q000517:prevention & control*; D020287:In Situ Nick-End Labeling; D008027:Light; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000528:radiation effects; D012374:Rod Cell Outer Segment / Q000528:radiation effects; D013997:Time Factors; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein
C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D004247:DNA