Mord3^NZW/LacJ
QTL Variant Detail

Summary

• QTL variant: Mord3^NZW/LacJ
• Name: modifier of retinal degeneration 3; NZW/LacJ
• MGI ID: MGI:3583112
• QTL: Mord3 Location: unknown Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: NZW/LacJ

Variant description

• Allele Type: QTL
• Inheritance: Dominant

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:99473

The gene Rpe65 is responsible for the QTL named Mord1. Inbred strain BALB/c carries a leu450 variant of Rpe65 that confers sensitivity to constant light-induced retinal damage (CLD). Inbred strain NZW/LacJ is also susceptible to CLD but carries the met450 Rpe65 variant that is associated with CLD resistance in albino strain C57BL/6J-Tyr^c-2J. An F2 intercross between NZW/LacJ and C57BL/6J-Tyr^c-2J was analyzed to determine if Rpe65 is truly associated with CLD sensitivity and if other QTL contribute tothis phenotype.

Linkage analysis was performed on 201 (NZW/LacJ x C57BL/6J-Tyr^c-2J)F2 intercross animals using markers at an average spacing of 16.5 cM. F2 animals between 95 to 105 days old were exposed to constant light for 4 weeks and sacrificed for phenotype analysis. Parental strain NZW/LacJ exhibits significantly greater optic nerve damage after constant light exposure compared to parental strain C57BL/6J-Tyr^c-2J. F1 hybrids exhibit resistance to CLD similar to C57BL/6J-Tyr^c-2J.

Highly significant linkage to CLD mapped to approximately 52 cM on mouse Chromosome 1 between D1Mit132 (43 cM) and D1Mit308 (62.1 cM) with LOD=5.22. This locus is named Mord2 (modifier of retinal degeneration 2). NZW/LacJ-derived alleles at Mord2 confer resistance to CLD with a recessive mode of inheritance. This locus accounts for 17% of the genetic variance. Potential candidate genes for Mord2 are Sag (53.6 cM) and Pde6d.

Significant linkage to CLD mapped to approximately 116 cM on mouse Chromosome 1 between D1Mit426 (101 cM) and D1Mit155 (112 cM) with LOD=3.26. This locus is named Mord3 (modifier of retinal degeneration 3). C57BL/6J-derived alleles at Mord3 confer resistance to CLD with a recessive mode of inheritance. This locus accounts for 11% of the genetic variance.

Rpe65 was not detected in this experiment thus supporting the CLD sensitive effect of the leu450 variant in BALB/c mice. This experiment proves the existence of additional modifying QTL for CLD sensitivity.

Suggestive resistance to CLD mappedto 10 cM on mouseChromosome 10 between D10Mit49 (2 cM) and D10Mit126 (21 cM) with LOD=1.98. C57BL/6J-derived alleles at this locus confer dominant resistance to CLD and accounts for 6% of the genetic variance. Suggestive resistance to CLD mapped to 66 cMon mouse Chromosome 13 between D13Mit213 (59 cM) and D13Mit78 (75 cM). NZW/LacJ-derived alleles at this locus confer recessive resistance to CLD and accounts for 6% of the genetic variance. Suggestive resistance to CLD mapped to 37 cM on mouse Chromosome14 between D14Mit68 (39 cM) and D14Mit75 (54 cM) with LOD=2.26. C57BL/6J-derived alleles at this locus confer additive resistance to CLD and account for 8% of the genetic variance. Suggestive resistance to CLD mapped to 13 cM on mouse Chromosome 16 between D16Mit107 and D16Mit60 with LOD=2.13. C57BL/6J-derived alleles at this locus confer additive resistance to CLD and account for 8% of the genetic variance.

References

• Original: J:99473 Danciger M, et al., Constant light-induced retinal damage and the RPE65-MET450 variant: assessment of the NZW/LacJ mouse. Mol Vis. 2005 May 27;11:374-9
• All: 1 reference(s)