The Laboratory mouse is one of the more commonly used animal models in retinitis pigmentosa research. Small size, rapid breeding and short generation time make this species - the E. coli of mammalian genetics - ideal for experimental research into the genetic mechanisms related to visual cell development, function and decay. These are phenomena which are basic to the understanding of cause, pathogenesis and eventually remedial measures of the human disease. Of the various genes known to affect the retina in mice, two - rd (retinal degeneration) and rds (retinal degeneration slow) - affect the photoreceptor cell specifically; and thus simulate some of the clinical features of the human disease. It has been often felt that availability of these mutant genes in characterized and uniform genetic background will vastly increase the resolving power of any analysis undertaken into these systems, especially analysis at the cellular and molecular level. Accordingly, a program was initiated and as a result of sustained effort over the last fifteen years, four lines of congenic mice which carry rd, rds, both rd and rds, and their normal alleles had been produced in normal agouti coloured C3H and albino BALB/c strains of mice. This research proposal has four main objectives - (1) To propagate by programmed breeding the eight different congenic lines of mice with different allelic combination at the rd and rds loci, (2) To produce by extension breeding adequate and appropriate animal resources to provide tissue samples with different but specific genotypic combination which will be made available to other investigators interested to use the mouse model, (3) To undertake new breeding programmes to examine the effects of other gene loci on the expression of the rd and the rds genes; thus expanding the genetic repertoire of the available materials, and (4) To study the degeneration process in retinal explants in tissue and organ culture set-ups with the eventual aim of developing genetically defined in vitro systems. 70% of the grant support will be used in the fulfilment of objectives 1 and 2, the rest for the objectives 3 and 4. Since this proposal is believed to be a modest one, and furthermore, since Bramus University Rotterdam will not charge overhead, the aims of this project can hoped to be realized in a very cost effective way.
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