Candidate genes for chromosomes 6 and 10 quantitative trait loci for age-related retinal degeneration in mice.

Purpose: In a previous study, several quantitative trait loci (QTL) that influence age-related degeneration (ageRD) were identified in a cross between the albino strains B6(Cg)-Tyr(c-2J)/J (B6a) and BALB/cByJ (C). The Chromosome (Chr) 6 and Chr 10 QTL were the strongest and most highly significant loci and both involved B6a protective alleles. The QTL were responsible for 21% and 9% of the variance in phenotypes, respectively.

Loss of the metalloprotease ADAM9 leads to cone-rod dystrophy in humans and retinal degeneration in mice.

Cone-rod dystrophy (CRD) is an inherited progressive retinal dystrophy affecting the function of cone and rod photoreceptors. By autozygosity mapping, we identified null mutations in the ADAM metallopeptidase domain 9 (ADAM9) gene in four consanguineous families with recessively inherited early-onset CRD. We also found reduced photoreceptor responses in Adam9 knockout mice, previously reported to be asymptomatic.

A missense mutation in the nuclear localization signal sequence of CERKL (p.R106S) causes autosomal recessive retinal degeneration.

Purpose: To investigate the genetic basis of autosomal recessive retinal degeneration in a large consanguineous family from Pakistan.

Methods: Ophthalmic examinations were conducted on family members to establish their diagnosis. Genomic DNA extracted from peripheral blood was used for homozygosity mapping to discover the chromosomal region that harbors the defective gene.

Influence of a quantitative trait locus on mouse chromosome 19 to the light-adapted electroretinogram.

Purpose: Both implicit time and amplitude of the cone-mediated electroretinographic (ERG) b-wave differ significantly between the C57BL/6JOlaHsd and 129S2/SvHsd inbred mouse strains. The purpose of this work was to undertake a quantitative genetics study to localize the gene or genes involved.

Methods: Implicit time and amplitude of the a- and b-waves of the single-flash and flicker cone-mediated ERG were recorded as the quantitative traits in reciprocal backcrossed populations.

Genetic modifiers of retinal degeneration in the rd3 mouse.

Purpose: 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.