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M. Danciger, L. Handschumacher, M.M. LaVail, S. Nusinowitz, H. Yang; The C57BL/6 Background Protects Against rd3 Retinal Degeneration . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3177.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Heckenlively et al (1993) showed that rd3 autosomal recessive retinal degeneration has a slower course in pigmented mice than in albino mice. Since the C57BL/6J–c2J (B6a) albino mouse is much more resistant to light–induced retinal damage than BALB/c and other albino mouse strains, we hypothesized that retinal degeneration (RD) caused by the rd3 mutation would progress more slowly in B6a than in BALB/c. To test this, we bred B6a and BALB/c mice congenic for the rd3 mutation and measured retinal morphology and function over the course of the disease. Methods: The Rb4Bnr–rd3/rd3 strain was mated to BALB/c and the F1's backcrossed to BALB/c to produce N2 mice. With successive backcrosses, N10 heterozygotes were bred and crossed to produce rd3/rd3 homozygotes. The rd3 allele was followed by PCR of tail DNA with markers that closely flank the mutant gene. The same breeding protocol was used for the albino B6a and the pigmented C57BL/6J (B6p) strains. RD was quantified in a single 1–µm section by averaging 54 measurements of the thickness of the outer nuclear layer (ONL) from far inferior to far superior through the optic nerve. Retinal function was quantified by measuring ERG maximum b–wave amplitude. Mice were kept in dim cyclic light. Results:N10, BALB/c, rd3/rd3 mice (C–rd3) progressed from an average ONL of 26.4 µm at 5 weeks to 6.3 µm at 12 weeks; the ERG was extinguished by 8 weeks. At 10 weeks, the ONL's of the C–rd3 congenics averaged 11.09 µm (n=20), the B6a–rd3/rd3 congenics (B6a–rd3) 19.17 µm (n=22) and the pigmented B6p–rd3/rd3 congenics (B6p–rd3) 24.38 µm (n=14). The t–test P values were 2.2 x 10–8 for C–rd3 vs. B6a–rd3 and 1.9 X 10–4 for B6a–rd3 vs. B6p–rd3. At 6 weeks, the average maximum b–waves of C–rd3, B6a–rd3 and B6p–rd3 were 33.79 µv (n=23), 90.88 µv (n=16) and 183.66 µv (n=19), respectively. The t–test P values were 7.8 x 10–7 for C–rd3 vs. B6a–rd3 and 1.7 x 10–7 for B6a–rd3 vs. B6p–rd3. Conclusions: Autosomal recessive retinal degeneration caused by the rd3 mutation progresses significantly more slowly in the light–resistant B6a albino background than in the light–sensitive BALB/c background, and even more slowly in the pigmented B6p background. Quantitative genetics studies are underway to identify the B6 alleles of the modifier genes that protect the retina from rd3 disease progression. Such genes may provide avenues of study for the treatment or prevention of human RD's.
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