The aims of this grant are (1 to place mutations affecting the retina in mice onto a few selected genetic backgrounds by standard breeding schedules, so that the gene actions can be more accurately compared and contrasted with one another, 2) to distribute affected and control mice or tissues or chemical extracts to qualified research scientists at no charge to them except for shipping costs, so that they can carry on their research without committing the time or bearing the expense of generating their own mice, and 3) to mutagenize male mice and mate them with females carrying known retinal mutations, so as to select for new mutant alleles that will illuminate how particular genes control retinal function and cause disease. Progeny of mutagenized mice will be screened for retinal disease by nondestructive indirect ophthalmoscopy, a rapid and effective method that markedly reduces the need to screen laboriously by expensive histological methods.These mouse models have been adding significantly to our understanding of inherited diseases of the retinitis pigmentosa category in humans, and are likely to contribute even more crucially in the years immediately ahead. The most widely used mutations at present are named retinal degeneration (rd), retinal degeneration slow (rds), Purkinje cell degeneration (pcd), and nervous (nr). We maintain each of these on several genetic backgrounds, including three independently-occurring mutant alleles at the pcd locus. We have developed, or are developing, most of these strains, and are the unique holder of several of them. Additionally, we will supply mice with new retinal disorders named hugger (hug), vitiligo (vit), and wabbler lethal-2J (wl2J); these affect not only retinal photoreceptor cells, the hallmark of the retinitis pigmentosa class of diseases, but also affect other components of the retina, and thus open the prospect of deepening our understanding of genetic control and functions of cells in retinal pigment epithelium and inner nuclear and ganglion cell layers. Further available mutants serve as models of congenital stationary night blindness. Still others cause hypopigmentation and developmental abnormalities in the trajectories of ganglion cell axons in the optic nerve. We are prepared also to advise other investigators, as we have done during the first funding cycle of this grant, concerning what mutants, genetic backgrounds, controls, ages, and numbers of mice might help to solve their research questions. Another service function will be to take on the propagation and dissemination of mutant stocks, including transgenic mice with retinal abnormalities, that are developed by other investigators who may not wish to remain solely responsible for holding and distributing such research material.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY006859-07
Application #
3263535
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1990-06-01
Project End
1995-11-30
Budget Start
1992-04-01
Budget End
1992-11-30
Support Year
7
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
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Lin-Jones, Jennifer; Parker, Ed; Wu, Mike et al. (2003) Disruption of kinesin II function using a dominant negative-acting transgene in Xenopus laevis rods results in photoreceptor degeneration. Invest Ophthalmol Vis Sci 44:3614-21
Duncan, T; Swint, C; Smith, S B et al. (1999) Levels of retinoic acid and retinaldehyde dehydrogenase expression in eyes of the Mitf-vit mouse model of retinal degeneration. Mol Vis 5:9
Bora, N; Defoe, D; Smith, S B (1999) Evidence of decreased adhesion between the neural retina and retinal pigmented epithelium of the Mitfvit (vitiligo) mutant mouse. Cell Tissue Res 295:65-75
Smith, S B; Zhou, B K; Orlow, S J (1998) Expression of tyrosinase and the tyrosinase related proteins in the Mitfvit (vitiligo) mouse eye: implications for the function of the microphthalmia transcription factor. Exp Eye Res 66:403-10
Smith, S B; Brodjian, S; Desai, S et al. (1997) Glial fibrillary acidic protein (GFAP) is synthesized in the early stages of the photoreceptor cell degeneration of the mivit/mivit (vitiligo) mouse. Exp Eye Res 64:645-50
Evans, B L; Smith, S B (1997) Analysis of esterification of retinoids in the retinal pigmented epithelium of the Mitf-vit (vitiligo) mutant mouse. Mol Vis 3:11
Tang, M; Ruiz, M; Kosaras, B et al. (1996) Increased cell genesis in retinal pigment epithelium of perinatal vitiligo mutant mice. Invest Ophthalmol Vis Sci 37:1116-24
Sidman, R L; Kosaras, B; Tang, M (1996) Pigment epithelial and retinal phenotypes in the vitiligo mivit, mutant mouse. Invest Ophthalmol Vis Sci 37:1097-115
Smith, S B; Titelman, R; Hamasaki, D I (1996) Effects of basic fibroblast growth factor on the retinal degeneration of the mi(vit)/mi(vit) (vitiligo) mouse: a morphologic and electrophysiologic study. Exp Eye Res 63:565-77

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