Degeneration of cone photoreceptors induced by expression of the Mas1 protooncogene.

Abstract:

:Although transgenic expression of oncogenes typically leads to tumorigenesis, oncogene expression directed to the rod photoreceptors leads to cell death without tumor formation. To evaluate the cellular and functional changes induced in cone photoreceptors by an oncogene, the Mas1 protooncogene was targeted to the cones of transgenic mice by the human red/green opsin promoter. Mas1 was chosen because of its exclusive expression in the nervous system and its homology to opsin. The overall histologic appearance of the transgenic retina was normal and retinal tumors were never observed. While rod-mediated electroretinograms were normal in all respects, cone-mediated responses were diminished in direct relationship to the level of transgene expression as determined by Northern blot analysis. Responses of UV- and green-sensitive cones were reduced equivalently, and Northern analysis and immunocytochemistry indicated that cone photoreceptor densities were markedly diminished throughout transgenic retinas. These results indicate that oncogene expression in cones induces cell death without tumor formation and support the possibility that aberrant oncogene expression may underlie some forms of hereditary retinal diseases. The Mas1 transgenic mice may be useful in understanding the cone photoreceptor degeneration that occurs in cone dystrophies and age-related macular degeneration and in evaluating potential therapies for these disorders.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Xu X,Quiambao AB,Roveri L,Pardue MT,Marx JL,Röhlich P,Peachey NS,Al-Ubaidi MR

doi

10.1006/exnr.2000.7370

keywords:

subject

Has Abstract

pub_date

2000-05-01 00:00:00

pages

207-19

issue

1

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(00)97370-9

journal_volume

163

pub_type

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