New retinal light damage QTL in mice with the light-sensitive RPE65 LEU variant

Mamm Genome. 2004 Apr;15(4):277-83. doi: 10.1007/s00335-003-2336-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Carrier Proteins
  • Chromosome Mapping
  • Crosses, Genetic
  • DNA / chemistry
  • DNA / genetics
  • Dinucleotide Repeats
  • Eye Proteins
  • Female
  • Leucine
  • Light / adverse effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Proteins / genetics*
  • Quantitative Trait Loci / genetics*
  • Retina / pathology
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / pathology
  • Rhodopsin / genetics
  • cis-trans-Isomerases

Substances

  • Carrier Proteins
  • Eye Proteins
  • Proteins
  • DNA
  • Rhodopsin
  • retinoid isomerohydrolase
  • cis-trans-Isomerases
  • Leucine