A QTL on distal chromosome 3 that influences the severity of light-induced damage to mouse photoreceptors.
C57BL/6J-c(2J) (c2J) albino mice showed much less damage to their photoreceptors after exposure to prolonged light than BALB/c mice and seven other albino strains tested. There were no gender differences, and preliminary studies suggested that the c2J relative protective effect was a complex trait. A genome-wide scan using dinucleotide repeat markers was carried out for the analysis of 194 progeny of the backcross (c2J x BALB/c)F(1) x c2J and the thickness of the outer nuclear layer (ONL) of the retina was the quantitative trait reflecting retinal damage. Our results revealed a strong and highly significant quantitative trait locus (QTL) on mouse Chromosome (Chr) 3 that contributes almost 50% of the c2J protective effect, and three other very weak but significant QTLs on Chrs 9, 12, and 14. Interestingly, the Chrs 9 and 12 QTLs corresponded to relative susceptibility alleles in c2J (or relative protection alleles in BALB/c), the opposite of the relative protective effect of the QTLs on Chrs 3 and 14. We mapped the Rpe65 gene to the apex of the Chr 3 QTL (LOD score = 19.3). Northern analysis showed no difference in retinal expression of Rpe65 message between c2J and BALB/c mice. However, sequencing of the Rpe65 message revealed a single base change in codon 450, predicting a methionine in c2J and a leucine in BALB/c. When the retinas of aging BALB/c and c2J mice reared in normal cyclic light were compared, the BALB/c retinas showed a small but significant loss of photoreceptor cells, while the c2J retinas did not. Finding light damage-modifying genes in the mouse may open avenues of study for understanding age-related macular degeneration and other retinal degenerations, since light exposures may contribute to the course of these diseases.
Danciger
M
M
Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, California 90095, USA. danciger@ucla.edu
Matthes
M T
MT
Yasamura
D
D
Akhmedov
N B
NB
Rickabaugh
T
T
Gentleman
S
S
Redmond
T M
TM
La Vail
M M
MM
Farber
D B
DB
D000375:Aging; D000818:Animals; D001483:Base Sequence; D002875:Chromosomes / Q000235:genetics*; D005260:Female; D005838:Genotype; D008027:Light; D008126:Lod Score; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018895:Microsatellite Repeats; D010786:Photoreceptor Cells / Q000473:pathology / Q000528:radiation effects*; D019655:Quantitative Trait, Heritable; D012160:Retina / Q000473:pathology / Q000528:radiation effects