Bax is not the heterodimerization partner necessary for sustained anti-photoreceptor-cell-death activity of Bcl-2.
OBJECTIVE
Ectopic expression of Bcl-2 in photoreceptors of certain mouse models of retinitis pigmentosa (RP) temporarily slows disease progression. The temporary effect produced by Bcl-2 may result from insufficient levels of functional complexes between Bcl-2 and additional proteins necessary for maintaining the anti-apoptotic activity of Bcl-2. Although the overexpression of Bax generally induces apoptosis, Bax exerts anti-apoptotic properties when complexed with Bcl-2 in certain cell culture systems. These studies were designed to determine whether coexpression of Bcl-2 and Bax would improve the neuroprotective effect provided by Bcl-2 alone in photoreceptors of mice with autosomal dominant RP (adRP).


METHODS
Transgenic mice were produced that overexpressed Bax and Bcl-2 specifically in photoreceptor cells, using the murine opsin promoter to drive transgene expression. These mice were crossed with an adRP mouse model to assess the effect of coexpression of Bax and Bcl-2 on retinal degeneration. Morphologic analysis was performed on retinas isolated at various developmental times to monitor disease progression.


RESULTS
Ectopic expression of Bax in photoreceptors resulted in extensive rod cell death dependent on the level of Bax transgene expression. Although Bcl-2 was able to inhibit Bax-induced photoreceptor cell death, the coexpression of Bcl-2 and Bax in photoreceptors of mice with adRP did not enhance the protective effect against photoreceptor cell death exerted by Bcl-2 alone.


CONCLUSIONS
Coexpression of Bax and Bcl-2, at the levels produced in the transgenic lines, does not extend the temporary neuroprotective effect produced by Bcl-2 in photoreceptors of mice with adRP.
Eversole-Cire
Pamela
P
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Chen
Jeannie
J
Simon
Melvin I
MI
D000818:Animals; D015153:Blotting, Western; D016923:Cell Death; D017931:DNA Primers / Q000737:chemistry; D019281:Dimerization; D015536:Down-Regulation; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000378:metabolism* / Q000473:pathology; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein