Arrd1^BALB/cByJ
QTL Variant Detail

Summary

• QTL variant: Arrd1^BALB/cByJ
• Name: age-related retinal degeneration 1; BALB/cByJ
• MGI ID: MGI:2664152
• QTL: Arrd1 Location: Chr6:75521339-92584431 bp Genetic Position: Chr6, Syntenic

Variant origin

• Strain of Specimen: BALB/cByJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers susceptibility to age-related retinal degeneration compared to C57BL/6J.
• Inheritance: Recessive

Notes

Candidate Genes

J:118199

Linkage analysis was performed on 170 animals from a (A/J x C57BL/6J)F2 intercross to determine if age-related retinal degeneration QTLs previously identified in a (C57BL/6J-Tyr^c-2J x BALB/cByJ)F2 intercross are present. Parental strain A/J exhibits greater age-related retinal degeneration compared to C57BL/6J. F2 animals were maintained in a dimly-lit environment and sacrificed at 8 months of age. The retinal outer nuclear layer was recorded for each animal. Eighty-six polymorphic markers at an average spacing of 13.1 cM were used for the genome scan.

Previously identified QTLs Arrd1 (chr6), Arrd2 (chr10), and Arrd3 (chr16) were not detected in this cross. However, SNP analysis was used to identify positional candidate genes for Arrd1 at 35 cM. Prokr1, Gkn1, Gata2 (38.5 cM) , 2010301N04Rik, and E230015B07Rik map to the Arrd1 interval and are expressed in the eye. Antxr, Ruvbl1, and Eefsec map to the Arrd1 locus but do not exhibit co-expression with retina- or RPE-specific genes.

Significant linkage to age-related retinal degeneration was detected on the X chromosome between DXMit192 (16 cM) and DXMit19 (43.2 cM). This locus is named Arrd4 (age-related retinal degeneration 4). Males hemizygous for C57BL/6J-derived alleles at Arrd4 exhibit decreased retinal degeneration compared to females with A/J-derived alleles. Thus, Arrd4 appears to have a sex-dependent effect.

Suggestive linkage to age-related retinal degeneration mapped to proximal mouse Chromosome 14 between D14Mit98 (3 cM) and D14Mit60 (15 cM) with LOD=2.15. This region overlaps with a suggestive locus detected in the (C57BL/6J-Tyr^c-2J x BALB/cByJ)F2 cross. C57BL/6J-derived alleles confer susceptibility retinal degeneration in both crosses.

Suggestive linkage was detected at 13 cM- 29 cM on mouse Chromosome 12 between D12Mit59 and D12Mit91 (LOD=2.24). This locus was also suggestive in the (C57BL/6J-Tyr^c-2J x BALB/cByJ)F2 cross between D12Mit60 (16 cM) and D12Mit236 (22 cM). C57BL/6J-derived alleles confer susceptibility to retinal degeneration in both crosses. A distal locus also shows suggestive linkage to retinal degeneration in (A/J x C57BL/6J)F2 animals at 53 cM - 59 cM (LOD=2.91). C57BL/6J-derived alleles at this locus confers susceptibility to retinal degeneration.

Suggestive linkage unique to the (A/J x C57BL/6J)F2 cross mapped to 35 cM (D13Mit13) - 40 cM (D13Mit256) on mouse Chromosome 13 (LOD=2.85) and 22.9 cM (D17Mit51) - 34.3 cM (D17Mit20) on mouse Chromosome 17 (LOD=2.22). C57BL/6J-derived alleles at these loci confer resistance to age-related retinal degeneration.

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

J:83546

86 markers at an average resolution of 15.7 cM were screened in 268 (BALB/cByJ x C57BL/6J-Tyr^c-2J)F2 animals to identify QTLs associated with age-related retinal degeneration. Parental strain BALB/cByJ exhibits greater retinal photoreceptor loss at 8 months of age compared to parental strain C57BL/6J-Tyr^c-2J.

A significant locus for age-related retinal degeneration, Arrd1, mapped to an interval spanning 32.5 cM - 37.5 cM on mouse Chromosome 6 with a peak LOD score of 13.5 between D6Mit209 and D6Mit284. C57BL/6J-derived alleles confer dominant resistance to retinal degeneration at Arrd1.

Arrd2 mapped to an interval spanning 11 cM - 21 cM on mouse Chromosome 10 with a peak LOD score of 6.4 between D10Mit213 and D10Mit126. C57BL/6J-derived alleles confer additively inherited resistance to retinal degeneration at Arrd2.

Arrd3 mapped to a broad interval spanning 23.4 cM - 55.2 cM on mouse Chromosome 16 with a peak LOD score of 7.1 between D16Mit60 and D16Mit139. BALB/cByJ-derived alleles confer dominant resistance to retinal degeneration at Arrd3.

Suggestive QTLs mapped to 5 cM on mouse Chromosome 14 with LOD=2.7 at D14Mit126, 38 cM on mouse Chromosome 18 with LOD=2.6 at D18Mit208, 16 cM on mouse Chromosome 12 with LOD=2.6 at D12Mit60, 24 cM on mouse Chromosome 13 with LOD=2.5 at D13Mit19, and 53 cM on mouse Chromosome 8 with LOD=2.1 at D8Mit47. C57BL/6J-derived alleles confer resistance to retinal degeneration at all loci except D12Mit60 where BALB/cByJ-derived alleles confer resistance.

References

• Original: J:83546 Danciger M, et al., A strong and highly significant QTL on chromosome 6 that protects the mouse from age-related retinal degeneration. Invest Ophthalmol Vis Sci. 2003 Jun;44(6):2442-9
• All: 1 reference(s)