Suppression of developmental retinal cell death but not of photoreceptor degeneration in Bax-deficient mice.
OBJECTIVE
Bax, a member of the Bcl2 family of cell death regulators, induces cell death by promoting the induction of apoptosis. Bax-deficient mice were examined in this study to determine whether Bax is required for cell death in the developing retina and for pathologic apoptotic photoreceptor degeneration resulting from the rd mutation.


METHODS
Retinas from Bax-deficient mice and their wild-type siblings were harvested at postnatal day (P) 7 and processed for TdT-dUTP terminal nick-end labeling (TUNEL) staining, and the number of nuclei containing fragmented DNA were counted. Adult retinas and optic nerves were processed for plastic-embedded 1-microm sections, and the cross-sectional area was determined. The mutant Bax allele was outbred onto the C3H mouse strain, which carries the rd allele. Retinas from these animals were examined histologically at P21 after most of the photoreceptor cell death had occurred.


RESULTS
At P7, around the time of peak cell death in the inner nuclear layer (INL), significantly fewer neurons in INL and ganglion cell layer (GCL) were TUNEL positive in Bax-deficient mice than in their wild-type siblings. In adult Bax-deficient mice, the cross-sectional area of the optic nerve was approximately 50% larger than in wild-type siblings, and the total number of retinal ganglion cell axons was increased to 226%. The INL of Bax-deficient mice was thicker than normal. The Bax genotype did not affect the thickness or histologic appearance of the outer nuclear layer in retinas of mice with wild-type or mutant rd alleles.


CONCLUSIONS
In the absence of the expression of the Bax gene, there is a profound increase in the survival of retinal ganglion cells that lasts into adulthood. Similarly, death of INL cells is diminished but not completely abolished. The absence of Bax does not, however, protect photoreceptors from naturally occurring cell death or degeneration induced by the rd mutation. This shows that Bax is involved to a variable degree in the control of developmental cell death in the retina and that not all apoptotic retinal cell deaths are controlled by Bax.
Mosinger Ogilvie
J
J
Central Institute for the Deaf, St. Louis, Missouri 63110, USA.
Deckwerth
T L
TL
Knudson
C M
CM
Korsmeyer
S J
SJ
D000818:Animals; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival; D004249:DNA Damage; D053938:DNA Fragmentation; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology; D009900:Optic Nerve / Q000473:pathology; D010786:Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency* / Q000235:genetics; D012160:Retina / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000473:pathology; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein