The @entity1105 represent a large and heterogenous group of hereditary neurodegenerations, for many of which, the molecular defect has been defined. However, the mechanism of cell death has not been determined for any form of @entity2000 . The @entity2000 slow (rds-/-) mutation of @entity19 is associated with nondevelopment of photoreceptor outer segments and gradual death of photoreceptor cell bodies, attributed to the absence of the outer segment protein rds/peripherin. Here, we examined the effects of a transgene encoding normal rds/peripherin that had integrated into the X-chromosome in male and female rds-/- mutant retinas. In 2-month-old transgenic males and homozygous-transgenic females on rds-/-, we observed virtually complete rescue of both the outer segment nondevelopment and @entity528 . In contrast, hemizygous-transgenic rds-/- female littermates showed patchy distributions of the transgene mRNA, by in situ hybridization analysis, and of photoreceptor cells that contain outer segments. This pattern is consistent with random inactivation of the X-chromosome and mosaic expression of the transgene. Surprisingly, we observed significant photoreceptor cell loss in both transgene-expressing and nonexpressing patches in hemizygous female retinas. These observations were supported by nuclease protection analysis, which showed notably lower than predicted levels of transgene mRNA in retinas from hemizygous females compared with male and homozygous female littermates. This phenotype suggests an important component of non-cell-autonomous photoreceptor death in rds-/- mutant @entity19 . These results have significance to both the etiology and potential treatment of @entity1 @entity2000 .

Non-cell-autonomous @entity528 in rds mutant XXXX mosaic for expression of a rescue transgene.

@entity1 :: ('9606', 'Species') :: ['human'] @entity2000 :: ('MESH:D012162', 'Disease') :: ['inherited retinal degenerations', 'retinal degeneration'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity1105 :: ('MESH:D058499', 'Disease') :: ['inherited retinal dystrophies'] @entity528 :: ('MESH:D009410', 'Disease') :: ['photoreceptor degeneration']
@entity19 :: (10090,Species) :: ['mice']
