title: New retinal light damage QTL in mice with the light-sensitive RPE65 LEU variant.
abstract: The purpose of this study was to determine the QTL that influence acute, light-induced retinal degeneration differences between the BALB/cByJ and 129S1/SvImJ mouse strains. Five- to 6-week-old F(2) progeny of an intercross between the two strains were exposed to 15,000 LUX of white light for 1 h after their pupils were dilated, placed in the dark for 16 h, and kept for 10-12 days in dim cyclic light before retinal rhodopsin was measured spectrophotometrically. This was used as the quantitative trait for retinal degeneration. Neither gender nor pigmentation had a significant influence on the amount of rhodopsin after light exposure in the F(2) progeny. For genetic study, DNAs of the 27-36 F(2) progeny with the highest and 27-36 F(2) with the lowest levels of rhodopsin after light exposure were genotyped with 71 dinucleotide repeat markers spanning the genome. Any marker with a 95% probability of being associated with phenotype was tested in all 289 F(2) progeny. Data were analyzed with Map Manager QTX. Significant QTL were found on mouse Chrs 1 and 4, and suggestive QTL on Chrs 6 and 2. The four QTL together equal an estimated 78% of the total genetic effect, and each of the QTL represents a gene with BALB/c susceptible alleles. The Chr 6 QTL is in the same region as a highly significant age-related retinal degeneration QTL found previously. Identification of these QTL is a first step toward identifying the modifier genes/alleles they represent, and identification of the modifiers may provide important information for human retinal diseases that are accelerated by light exposure.
authors.affiliation: Department of Biology, Loyola Marymount University, Los Angeles, California 90045-2659, USA. mdancige@lmu.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Danciger
authors.forename: Jessica
authors.initials: J
authors.lastname: Lyon
authors.forename: Danielle
authors.initials: D
authors.lastname: Worrill
authors.forename: Sara
authors.initials: S
authors.lastname: Hoffman
authors.forename: Janis
authors.initials: J
authors.lastname: Lem
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Reme
authors.forename: Andreas
authors.initials: A
authors.lastname: Wenzel
authors.forename: Christian
authors.initials: C
authors.lastname: Grimm
mesh_terms: D000483:Alleles; D000818:Animals; D002352:Carrier Proteins; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004247:DNA / Q000737:chemistry / Q000235:genetics; D018900:Dinucleotide Repeats; D005136:Eye Proteins; D005260:Female; D007930:Leucine; D008027:Light / Q000009:adverse effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D012160:Retina / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology; D012243:Rhodopsin / Q000235:genetics; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D004247:DNA; D005136:Eye Proteins; D007930:Leucine; D011506:Proteins; D012243:Rhodopsin; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase