Article

Genetic modifiers of retinal degeneration in the rd3 mouse.

Department of Biology, Loyola Marymount University, Los Angeles, California 90045-2659, USA.
Investigative ophthalmology & visual science (impact factor: 3.43). 08/2008; 49(7):2863-9. DOI:10.1167/iovs.08-1715 pp.2863-9
Source: PubMed

ABSTRACT 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.
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.
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.
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.

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Keywords

Additional studies
 
B6a-rd3/rd3 congenic strains
 
B6a-rd3/rd3 strains
 
critical intervals
 
F2 BALB-
 
follow-up SNPs
 
hundred forty-eight SNPs
 
Inherited Disease Research
 
inherited RD
 
LRD studies
 
modulate rd3-RD
 
partial commonality
 
previous studies
 
RD diseases
 
RD-modifying quantitative trait loci
 
rd3 disease
 
rd3 QTLs
 
Significant QTLs
 
strongest QTLs
 
Suggestive QTLs
 

Michael Danciger