Genetic modifiers of retinal degeneration in the rd3 mouse

¹ Department of Biology, Loyola Marymount University, 7900 Loyola Boulevard, Los Angeles, California, 90045-8220, United States
² Department of Biology, Loyola Marymount University, Los Angeles, California, United States
³ Beckman Vision Center, UCSF School of Medicine, San Francisco, California, United States
⁴ University of Tennessee at Memphis, Memphis, Tennessee, United States

^* To whom correspondence should be addressed. E-mail: hmdanciger{at}yahoo.com.

	Abstract

Purposes: In previous studies of light-induced (LRD) and age-related (ageRD) retinal degeneration (RD) between the BALB/cByJ (BALB) and B6(Cg)-Tyrc-2J/J (B6a) albino mouse strains, we identified RD-modifying quantitative trait loci (QTL). After breeding BALB- and B6a-rd3/rd3 congenic strains, and finding significant differences in RD, we performed an F1 intercross to determine rd3 QTL that influence this inherited RD. Methods: N10, F2 BALB- and B6a-rd3/rd3 strains were measured for retinal outer nuclear layer (ONL) thickness from 5 to 12 weeks of age. Since 10 weeks showed significant differences in the ONL, F2 progeny from an F1 intercross were measured for ONL thickness. F2 DNAs were genotyped for SNPs by the Center for Inherited Disease Research. Correlation of genotype with phenotype was made with Map Manager QTX. Results: 148 SNPs ~10 cM apart were typed in the F2 progeny and analyzed. Significant QTL were identified on Chrs 17, 8, 14 and 6 (B6a alleles protective) and two on Chr 5 (BALB alleles protective). Suggestive QTL were found as well. For the strongest QTL, follow-up SNPs were analyzed to narrow the critical intervals. Additional studies demonstrated that rd3 disease is exacerbated by light but not protected by the absence of rhodopsin regeneration. Conclusions: QTL were identified that modulate rd3-RD. These overlapped some QTL from previous ageRD and LRD studies. The presence of some of the same QTL in several studies suggests partial commonality in RD pathways. Identifying natural gene/alleles that modify RDs opens avenues of study that may lead to therapies for RD diseases.

Key Words: retinal degeneration, genetic diseases, light damage, complex genetics, QTL, mouse

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