Morq1^C3H/Rl
QTL Variant Detail

Summary

• QTL variant: Morq1^C3H/Rl
• Name: modifier of Rs1 QTL 1; C3H/Rl
• MGI ID: MGI:3784603
• QTL: Morq1 Location: Chr7:97551681-97551791 bp Genetic Position: Chr7, Syntenic

Variant origin

• Strain of Specimen: C3H/Rl

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers susceptibility to Rs1^tmcg1-associated retinal schisis compared to AKR/J. (J:133513)
• Inheritance: Dominant

Notes

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

J:133513

Linkage analysis was performed to identify genetic modifiers of X-linked retinoschisis associated with the Rs1^tmgc1 mutation. This mutation was generated by ENU mutatgenesis on a mixed C57BL/6JRn and C3H/Rl genetic background. Females homozygous for Rs1^tmgc1 and hemizygous males display severe retinal schisis at 4 weeks of age gradually disappearing by 10 weeks of age. A population of 270 (AKR/J x STOCK-Rs1^tmgc1)F2 male animals were genotyped at 80 polymorphic loci. The F2 animals displayed considerable variability in the retinal schisis phenotype.

Significant linkage was detected at chromosome 7. Fine-mapping with addition markers resulted in peak linkage at 48.5 cM with LOD=17.2 at D7Mit321. This locus is named Morq1 (modifier of Rs1 QTL 1).AKR/J-derived alleles at Morq1 confer recessively inherited resistance to retinal schisis, while C57BL/6JRn- and C3H/Rl-derived alleles at Morq1 confer susceptibility. Authors suspect epistatic interaction between Rs1 and Morq1.

The existence of Morq1 was confirmed using congenic line analysis. B6.Cg-Rs1^tmgc1 congenic animals display 37% incidence of retinal schisis. When the Mor1^AKR/J allele is present the incidence of retinal schisis drops to 0%. Interestingly, C3H.Cg-Rs1^tmgc1 congenic animals display significant susceptibility to retinal schisis with 92% incidence. Penetrance of Rs1^tmcg1 appears to differ on the C57BL/6JRn and C3H/Rl genetic backgrounds.

The Morq1 QTL interval is a 9 cM region flanked by D7Mit279 (37 cM) and D7Mit237 (52.8 cM) and contains roughly 635 genes. Potential candidate genes for Morq1 include Dlg2 (47.6 cM), Tmem126a, Tmem126b, Tmem135, Odz4 (47.7 cM), Tsku, and Fdz4.

References

• Original: J:133513 Johnson BA, et al., Genetic modification of the schisis phenotype in a mouse model of x-linked retinoschisis. Genetics. 2008 Mar;178(3):1785-94
• All: 2 reference(s)