Mapping of genetic modifiers of Nr2e3
rd7/rd7
that suppress retinal degeneration and restore blue cone cells to normal quantity |
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Authors: | Neena B Haider Weidong Zhang Ron Hurd Akihiro Ikeda Arne M Nystuen Jürgen K Naggert Patsy M Nishina |
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Institution: | (1) Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA;(2) Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA;(3) The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA;(4) Department of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA;(5) 985805 Nebraska Medical Center, Omaha, NE 68198-5805, USA |
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Abstract: | The retinal degeneration 7 (rd7) mouse, lacking expression of the Nr2e3 gene, exhibits retinal dysplasia and a slow, progressive degeneration due to an abnormal production of blue opsin-expressing
cone cells. In this study we evaluated three strains of mice to identify alleles that would slow or ameliorate the retinal
degeneration observed in Nr2e3
rd7/rd7
mice. Our studies reveal that genetic background greatly influences the expression of the Nr2e3
rd7/rd7
phenotype and that the inbred mouse strains CAST/EiJ, AKR/J, and NOD.NON-H2
nb1
carry alleles that confer resistance to Nr2e3
rd7/rd7
-induced retinal degeneration. B6.Cg-Nr2e3
rd7/rd7
mice were outcrossed to each strain and the F1 progeny were intercrossed to produce F2 mice. In each intercross, 20–24% of the total F2 progeny were homozygous for the Nr2e3
rd7/rd7
mutation in a mixed genetic background; approximately 28–48% of the Nr2e3
rd7/rd7
homozygotes were suppressed for the degenerative retina phenotype in a mixed genetic background. The suppressed mice had
no retinal spots and normal retinal morphology with a normal complement of blue opsin-expressing cone cells. An initial genome
scan revealed a significant association of the suppressed phenotype with loci on chromosomes 8 and 19 with the CAST/EiJ background,
two marginal loci on chromosomes 7 and 11 with the AKR/J background, and no significant QTL with the NOD.NON-H2
nb1
background. We did not observe any significant epistatic effects in this study. Our results suggest that there are several
genes that are likely to act in the same or parallel pathway as NR2E3 that can rescue the Nr2e3
rd7/rd7
phenotype and may serve as potential therapeutic targets.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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