Rgcs1^BALB/cByJ
QTL Variant Detail

Summary

• QTL variant: Rgcs1^BALB/cByJ
• Name: retinal ganglion cell susceptible 1; BALB/cByJ
• MGI ID: MGI:3823251
• QTL: Rgcs1 Location: Chr5:55388334-108762627 bp Genetic Position: Chr5, Syntenic

Variant origin

• Strain of Specimen: BALB/cByJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers susceptibility to retinal ganglion cell degeneration after optic nerve injury compared to DBA/2J. (J:142950)
• Inheritance: Recessive

Notes

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

J:142950

Linkage analysis was performed on 196 (BALB/cByJ x DBA/2J)F2 animals to identify genetic loci affecting resistance to retinal ganglion cell degeneration. Experimental animals were subjected to optic nerve crush at 8 weeks of age and phenotyped for retinal ganglion cell survival after 3 weeks. Parental strain DBA/2J is resistant to retinal ganglion cell death compared to parental strain BALB/cByJ. A panel of 65 polymorphic markers spaced approximately 20 cM apart was used for the genome scan. The population of F2 animals analyzed included the 60 most resistant and 49 most susceptible to retinal ganglion cell death.

Significant linkage mapped to mouse Chromosome 5 between 34 cM (D5Mit254) and 59 cM (D5Mit338). Peak linkage to retinal cell ganglion degeneration occurs as 38 cM with LOD=5.825. This locus accounts for 11.61% of the phenotypic variance and is named Rgcs1 (retinal ganglion cell susceptible 1). BALB/cByJ-derived alleles at Rgcs1 confer increased retinal ganglion cell death after optic nerve crush injury with a recessive mode of inheritance.

Seven potential candidate genes for Rgcs1 were identified in the QTL interval using various screening methods such as retinal cell gene expression assay and SNP association. Pcdh7 displays enriched expression in the retinal ganglion cell layer. Tlr1 (37 cM) and Tlr6 (37 cM) are both expressed in the retinal cell layer and display coding region SNP between parental strains. In addition, Tlr6 shows association with susceptibility to retinal ganglion cell degeneration across other inbred strains. Uchl1 (36 cM) displays enriched expression in the retina and is an eQTL associated with neurodegeneration susceptibility. Sparcl1 at 55 cM displays enriched expression in the retina, coding region SNP between parental strains, and possible association to retinal degeneration susceptibility across other inbred strains. Cplx1 displays enriched expression in the retina and is possibly associated with secondary neurodegeneration mediated by glutamate toxicity. Hspb8 (59cM) is expressed in the retina and may be associated with neurodegeneration susceptibility. Further investigation is required to narrow the Rgcs1 QTL region and refine candidate genes.

Suggestive linkage to retinal ganglion cell degeneration mapped to 3.5 cM on chromosome 6 with LOD=3.045 at D6Mit83.

References

• Original: J:142950 Dietz JA, et al., Rgcs1, a dominant QTL that affects retinal ganglion cell death after optic nerve crush in mice. BMC Neurosci. 2008;9:74
• All: 2 reference(s)