The goal of this research program is to develop an in vitro assay for the functional characterization of the retina-specific ABC transporter, ABCR/RIM. Mutations in the gene encoding ABCR/RIM are responsible for Stargardt disease (STGD), an autosomal recessive early onset form of macular degeneration, and have also been reported in a subset of patients with age related macular degeneration (AMD). Unpublished data implicate other mutations in this gene in some cases of autosomal recessive retinitis pigmentosa (RP).
We aim to (1) identify the transported substrate and (2) develop methods for producing recombinant human ABCR/RIM that can be used to test the effect of mutations on the structure, function, and stability of this protein. Identifying the transported molecule(s) may reveal new compounds or new roles for known compounds. Determining whether the transported molecule is transported in conjunction with specific binding proteins, and studying its synthesis, degradation, and processing may lead both to the identification of additional candidate genes for retinal diseases, and to the identification of additional targets for drug development. Production of a large number of different ABCR/RIM proteins, each carrying a mutation found in humans with STGD, AMD, or RP will allow us to determine the biochemical defect in each case, and will allow a correlation to be drawn between the clinical characteristics of the affected subjects and the biochemical defects resulting from the mutations they carry.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY012362-01
Application #
2739194
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1999-01-01
Project End
2003-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218