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.
Hahn
P
P
FM Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, PA, USA.
Lindsten
T
T
Lyubarsky
A
A
Ying
G-S
GS
Pugh
E N
EN
Thompson
C B
CB
Dunaief
J L
JL
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