Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  5
• Reference
  J:215026 Dietz JA, et al., Spink2 modulates apoptotic susceptibility and is a candidate gene in the Rgcs1 QTL that affects retinal ganglion cell death after optic nerve damage. PLoS One. 2014;9(4):e93564
• ID
  MGI:6151436

Genes

Gene	Assay Type
Rgcs1	visible phenotype
Spink2

Notes

• Experiment
  Rgcs1 is a quantitative trait locus, on mouse chromosome 5, that influences susceptibility of retinal ganglion cells to acute damage of the optic nerve. Normally resistant mice (DBA/2J) congenic for the susceptible allele from BALB/cByJ mice exhibit susceptibility to ganglion cells, not only in acute optic nerve crush, but also to chronic inherited glaucoma that is characteristic of the DBA/2J strain as they age.
  
  In the current study the Rgcs1 QTL region of chromosome 5, flanked by microsatellite markers D5Mit254 (34 cM) and D5Mit338 (59 cM), was bred onto the DBA/2J background through 10 successive generations creating substrain D2.CBy-(D5Mit254-D5Mit338)/J (D2.CBy-Rgcs1). Substrain mice, heterozygous and homozygous for the BALB/cByJ locus were then subjected to the optic nerve crush procedure at 8 weeks of age and compared to pure bred DBA/2J animals.
  
  DBA/2J mice congenic for the BALB/cByJ Rgcs1 allele ((D2.CBy-Rgcs1) developed increased introcular pressure (IOP) with age, equivalent to IOP changes in DBA/2J animals The congenic mice, however, had more severe glaucomatous damage to both the optic nerve and retina, compared with pure bred and heterozygous age matched mice. The results supported the hypothesis that the Rgcs1 locus can modify the level of glaucomatous damage in a manner consistent with the acute optic nerve damage paradigm.
  
  The Rgcs1 region was originally identified using microsatellite markers to screen a mapping population of 100 F2 mice selected from the extreme phenotypes of the larger population of 196 animals. For SNP mapping, the entire F2 population of mice was used, including an additional 56 individuals for a total of 252 mice. In the first screen, a total of 37 SNPs located between 34 and 59 cM (the original region defining the Rgcs1 allele) were used. A second screening further refined the significant association, with a peak LOD score of 6.81, centered between 76.7 and 77.7 Mb (Fig 3).
  
  The dominant inheritance pattern of the resistant phenotype was a function of the rs13478335 SNP. F2 animals, homozygous for the BALB/cByJ allele (CC), had significantly more cell loss than mice either homozygous or heterozygous for the DBA/2J allele (DD and DC). Overall, the allele accounted for 11% of the cell death phenotype after optic nerve crush.
  
  The 1 Mbp region of Rgcs1 identified by SNP mapping contained 23 open reading frames identified as genes and 3 pseudogenes. Strain comparison analysis of the region using the mouse genomes database (Wellcome Trust Sanger Institute) revealed a 220 bp deletion in intron 1 of the Spink2 gene of BALB/cByJ which could affect expression levels. Sequence analysis of multiple Spink2 cDNA clones isolated from DBA/2J and BALB/cByJ mice revealed a single A/T polymorphism in exon 2.