Purchase this article with an account.
M. Danciger, H. Yang, J.E. Lyon, D.M. Worrill, M.M. LaVail; Highly Significant QTLs on Mouse Chromosomes 6, 10 and 16 that Strongly Influence Age-related Retinal Degeneration; Comparison with Light Damage QTLs . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2021.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: C57BL/6J-c2J (c2J) albino mice undergo significantly less retinal degeneration than BALB/cByJ albinos during aging in dim cyclic light. The purpose of this work was to identify by quantitative genetics the chromosomal loci (QTLs) of the genes/alleles that influence age-related retinal degeneration in mice (ARD) for two main reasons: 1) to take the first step toward identifying mouse ARD genes and the human orthologs which may provide candidates for study in human age-related macular degeneration (AMD) and 2) to compare ARD QTLs with light-induced retinal degeneration QTLs identified in other studies. Methods: After aging in cyclic light for 8 months, the thickness of the outer nuclear layer of the retina was measured as the quantitative trait in 268 F2 progeny of an intercross between c2J and BALB/c mice. Genomic DNAs from the F2 progeny were genotyped with a large number of dinucleotide repeat markers comprising a genome-wide scan with an average spacing of 15.7 cM. The data were analyzed with the Map Manager QTX program. Results: Three strong and highly significant QTLs influencing ARD were detected. Two on mouse Chrs 6 and 10 represented c2J gene alleles that protected against ARD while the third on Chr 16 represented a c2J susceptibility allele. Several suggestive, weak QTLs were also found along with a gender-related effect. A comparison was made with a light-induced retinal degeneration (LRD) study involving these same two strains. The RPE65/MET450 variant which had a major influence on LRD, had no influence on ARD, and the major Chrs 10 and 16 ARD QTLs had little or no influence on LRD. However, at least one of the suggestive QTLs on Chr 12 that weakly influenced ARD also weakly influenced LRD. The dominant c2J, Chr 6 ARD QTL could not be compared because of the study design of the LRD backcross. However, in another quantitative genetics study of LRD between the 129S1/SvImJ and BALB/cByJ strains, a QTL with a significant effect was found in the same Chr 6 region as the ARD QTL. Conclusions: None of the chromosomal loci associated with ARD were homologous to human loci so far implicated in AMD. Therefore, these QTLs represent the first step toward identifying new candidate AMD genes for evaluation. In addition, our data indicate that substantial portions of the genetics of age-related and light-induced retinal degeneration are distinct from one another. On the other hand, the two types of degeneration may also have significant genetic elements in common.
This PDF is available to Subscribers Only