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H. Yang, L. Handschumacher, M.M. LaVail, M. Danciger; A Quantitative Genetics Study of Age–Related Retinal Degeneration Between the A/J and C57BL/6 Mouse Strains . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3819.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: In a previous quantitative genetics study of age–related retinal degeneration (ARRD) between the albino mouse strains BALB/c (C) and C57BL/6J–c2J (B6a), we found major QTL on Chrs 6, 10 and 16. Having determined that the A/J albino strain undergoes significantly more retinal degeneration as it ages than the C57BL/6J pigmented strain (B6), we have now conducted a second ARRD study with these two strains for two purposes: 1) to determine if the same or new QTL are present (repeated QTL represent the opportunity to determine if candidate gene differences segregate according to phenotype and new QTL represent new genes that influence ARRD); and 2) to determine if eye pigmentation has an influence on ARRD. Methods:The A/J strain was mated to B6 and the F1's intercrossed to produce 171 F2 mice. F2 mice were intercrossed to produce an additional 84 F3 mice. The F3 cross was produced to provide verification of major QTL found in the F2 cross. ARRD was quantified at 8 mos. of age in a single 1–µm retinal section by averaging 54 measurements of the thickness of the outer nuclear layer (ONL) from far inferior to far superior retina through the optic nerve. Mice were raised in 12:12 dim cyclic light with an in cage illuminance of 2–7 ft.–c. Dinucleotide repeat markers polymorphic between the B6 and A strains were genotyped by PCR of liver DNA. The Map Manager QT program was used to identify QTL. Results: Control A/J (n=9) and B6 (n=13) ONL averaged 28.80 µm and 41.59 µm, respectively (P = 1.01 x 10–11; t–test). Pigmented F2 progeny ONL (n=120) averaged 39.87 µm and albino F2 ONL 39.96 µm (NS). Male F2 ONL (n=94) averaged 40.48 µm and female F2 ONL (n=77) 39.06 µm (P = 8.69 x 10–4). Markers tested at the three major QTL of the previous study showed no QTL at Chrs 10 and 16 and a weak QTL at Chr 6. Interestingly, the Chr 6 QTL was protective for the A/J allele. Conclusions: There was no significant difference between pigmented and albino F2 mice in ARRD at 8 mos. However, just as we found in the previous B6a x C study, male and female A/J x B6 F2 progeny show a difference. The major QTL on Chrs 10 and 16 from the previous study were absent from this study while the Chr 6 QTL was present but weak. Therefore, QTL in other new chromosomal regions must be responsible for the remaining large difference in ARRD between the A/J and B6 strains. Identification of the genes that these QTL represent may open avenues of study leading to gene or pharmaceutical therapies for human retinal degenerations including AMD.
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