May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
A quantitative genetics retinal light damage study of a cross between one resistant and one sensitive albino mouse strain each with the RPE65–MET450 variant shows no QTL at the Rpe65 locus.
Author Affiliations & Notes
  • M. Danciger
    Biology, Loyola Marymount University, Los Angeles, CA
  • D. Worrill
    Biology, Loyola Marymount University, Los Angeles, CA
  • J. Lyon
    Biology, Loyola Marymount University, Los Angeles, CA
  • T. Hill
    Biology, Loyola Marymount University, Los Angeles, CA
  • H. Yang
    Beckman Vision Center, UCSF School of Medicine, San Francisco, CA
  • M.M. LaVail
    Beckman Vision Center, UCSF School of Medicine, San Francisco, CA
  • Footnotes
    Commercial Relationships  M. Danciger, None; D. Worrill, None; J. Lyon, None; T. Hill, None; H. Yang, None; M.M. LaVail, None.
  • Footnotes
    Support  Grants from the NIH (EY13280 and EY01919), RPB, FFB and MVRF
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 3716. doi:
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      M. Danciger, D. Worrill, J. Lyon, T. Hill, H. Yang, M.M. LaVail; A quantitative genetics retinal light damage study of a cross between one resistant and one sensitive albino mouse strain each with the RPE65–MET450 variant shows no QTL at the Rpe65 locus. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3716.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Previously, we showed that ∼ 50% of the genetic resistance to constant light–induced retinal damage exhibited by the C57BL/6J–c2J (B6–c2J) albino mouse relative to the BALB/c albino is due to a B6–c2J gene allele on distal Chr 3. A strong case has been made that the MET450 variant of RPE65 is that resistant allele. However, the NZW albino mouse is as susceptible to retinal light insult as other albino strains bearing the sensitive LEU450 variant of RPE65, yet NZW has MET450. One explanation for this is that the NZW strain has sensitive alleles of other genes that negate the protection conferred by RPE65–MET450. If this is so, there should be no quantitative trait locus (QTL) at distal Chr 3 in a retinal light damage study of a test cross between these two strains, and there should be other QTLs to explain the difference. The purpose of the work was to test the above hypothesis, and to uncover the other QTLs as a first step toward identifying the corresponding genes. Methods: 156 F2 progeny of an F1 intercross between the NZW and B6–c2J strains aged to approximately 3 months were exposed to 3 weeks of constant light at an in–cage luminance of 20–70 ft–c. After exposure, retinal damage was quantitated in a single 1–µm retinal section by averaging 12 measurements of the thickness of the outer nuclear layer in the posterior, superior retina. DNAs were genotyped with 77 dinucleotide repeat markers spanning the genome. Any marker with a 95% probability of being associated with phenotype or interacting with other markers was tested in 45 additional F2 progeny. Results: There was no QTL at distal Chr 3. There were QTLs on Chrs 1 (two), 10, 13, 14 and 16 and three significant interactions between pairs of markers. Both QTLs on Chr 1 matched QTLs found in previous retinal light damage studies, and the Chr 10 QTL matched an age–related retinal degeneration QTL. Each of the three matching QTLs from other studies involved at least one mouse strain different from B6–c2J or NZW. Conclusions: The absence of a QTL at distal Chr 3 in a cross between two albino mice with different sensitivities to retinal light damage yet carrying the MET450 variant supports the hypothesis that RPE65 is responsible for the Chr 3 QTL found previously. The matching of three QTLs from this study with QTLs in other studies suggests some commonality in retinal damage pathways, and offers the possibility to test candidate genes for co–segregation of genetic variant with phenotypic effect in several different strains.

Keywords: gene modifiers • retina • degenerations/dystrophies 
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