Genetic modifiers of retinal degeneration in the rd3 mouse.
OBJECTIVE
In previous studies of light-induced (LRD) and age-related (ageRD) retinal degeneration (RD) between the BALB/cByJ (BALB) and B6(Cg)-Tyr(c-2J)/J (B6a) albino mouse strains, RD-modifying quantitative trait loci (QTLs) were identified. After breeding BALB- and B6a-rd3/rd3 congenic strains and finding significant differences in RD, an F1 intercross to determine rd3 QTLs that influence this inherited RD was performed.


METHODS
N10, F2 BALB- and B6a-rd3/rd3 strains were measured for retinal outer nuclear layer (ONL) thickness from 5 to 12 weeks of age. Since 10 weeks showed significant differences in the ONL, F2 progeny from an F1 intercross were measured for ONL thickness. F2 DNAs were genotyped for SNPs by the Center for Inherited Disease Research. Correlation of genotype with phenotype was made with Map Manager QTX.


RESULTS
One hundred forty-eight SNPs approximately 10 cM apart were typed in the F2 progeny and analyzed. Significant QTLs were identified on chromosomes (Chrs) 17, 8, 14, and 6 (B6a alleles protective) and two on Chr 5 (BALB alleles protective). Suggestive QTLs were found as well. For the strongest QTLs, follow-up SNPs were analyzed to narrow the critical intervals. Additional studies demonstrated that rd3 disease is exacerbated by light but not protected by the absence of rhodopsin regeneration.


CONCLUSIONS
QTLs were identified that modulate rd3-RD. These overlapped some QTLs from previous ageRD and LRD studies. The presence of some of the same QTLs in several studies suggests partial commonality in RD pathways. Identifying natural gene/alleles that modify RDs opens avenues of study that may lead to therapies for RD diseases.
Danciger
Michael
M
Department of Biology, Loyola Marymount University, Los Angeles, California 90045-2659, USA. mdancige@lmu.edu
Ogando
Diego
D
Yang
Haidong
H
Matthes
Michael T
MT
Yu
Nicole
N
Ahern
Kelly
K
Yasumura
Douglas
D
Williams
Robert W
RW
Lavail
Matthew M
MM
D000818:Animals; D033481:Chromosomes, Mammalian; D005123:Eye / Q000378:metabolism; D005838:Genotype; D008027:Light; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012168:Retinal Pigments / Q000378:metabolism; D012243:Rhodopsin / Q000378:metabolism; D013045:Species Specificity
D012168:Retinal Pigments; D012243:Rhodopsin