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A Strong and Highly Significant QTL on Chromosome 6 that Protects the Mouse from Age-Related Retinal Degeneration

¹From the Department of Biology, Loyola Marymount University, Los Angeles, California; and ²Beckman Vision Center, University of California San Francisco School of Medicine, San Francisco, California.

PURPOSE. BALB/cByJ (C) albino mice have significantly more retinal degeneration as they age than C57BL/6J-c^2J (B6) albinos. To discover the genetic loci that influence age-related retinal degeneration (ARD), a quantitative genetics study was performed with 8-month-old progeny from an intercross between these two strains.

METHODS. The thickness of the outer nuclear layer of the retina was used as the quantitative trait. A genome-wide scan was performed with 86 genetic markers at an average distance of 15.7 cM. Map Manager QTX was used to analyze the data.

RESULTS. Three highly significant quantitative trait loci (QTLs) were detected on mouse chromosomes (Chrs) 6, 10, and 16. The B6 alleles were protective against ARD in the first two, and the C allele was protective in the third. Several suggestive, weak QTLs were also found, along with a gender-related effect. The strongest and most highly significant QTL on Chr 6 accounted for 30% of the total genetic effect with a LOD score of 13.5. The RPE65/MET450 variant of major influence on constant light-induced retinal degeneration (LRD) in a previous study of these same two mouse strains had no influence on ARD, and only some of the weak, suggestive QTLs influencing ARD were also observed in LRD.

CONCLUSIONS. Because none of the ARD QTLs was homologous to human chromosomal loci so far implicated in age-related macular degeneration, each represents a new candidate gene for potential study. The gene represented by the Chr 6 QTL is of particular interest because it has broad influence, very high significance, and a B6 allele that protects against ARD.

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