Aod3^A/J
QTL Variant Detail

Summary

• QTL variant: Aod3^A/J
• Name: autoimmune ovarian dysgenesis 3; A/J
• MGI ID: MGI:2670906
• QTL: Aod3 Location: unknown Genetic Position: Chr1, cM position of peak correlated region/allele: 50.34 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: A/J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased oophoritis severity and ovarian atrophy compared to C57BL/6J. (J:78005)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Interaction between Aod3 and Aod1, and between Aod3 and Gasa2, Aod5, and H2, appears to affect the oophoritis phenotype.

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

J:78005

Linkage analysis was performed on a population of (C57BL/6J x A/J)F1 x C57BL/6J backcross animals using 245 microsatellite markers at a resolution of 20 cM to identify QTLs associated with autoimmune ovarian dysgenesis (AOD). Parental strain A/J is susceptible and develops AOD 3 days after thymectomy whereas C57BL/6J is resistant.

Previously mapped QTLs Aod1 (on chromosome 16) and Aod2 (on chromosome 3) were detected in this study. Segregation distortion was observed for the Aod1 region on chromosome 16at 23 cM. Novel loci named Aod3, Aod4, and Aod5 were identified on mouse Chromosomes 1, 2, and 7 respectively.

Aod3 maps to 63 cM on mouse Chromosome 1 and is linked to oophoritis severity at D1Mit417 and to ovarian atrophy at D1Mit45. A/J-derived alleles confer increased susceptibility to AOD phenotypes at this locus. Aod3 contributes to 14% of the variance in oophoritis severity, and to 16% of the variance in ovarian atrophy. Linkage analysis using AXB and BXA recombinant inbred lines (RIL) also confirmed the presence of Aod3. Interaction between Aod3 and Aod1, and between Aod3 and Gasa2, Aod5, and H2, appears to affect the oophoritis phenotype.

Aod4 maps to 79 cM on mouse Chromosome 2 and is linked to ovarian atrophy at D2Mit452. A/J-derived allelesconfer increased susceptibility ovarian atrophy at this locus. Aod4 contributes about 16% of the phenotypic variance. Interaction between Aod4 and Aod1 appears to influence oophoritis severity and ovarian dystrophy, and interaction between Aod4 and Aod2 appears to influence anti-ovarian autoantibody production.

Aod5 maps to 1.1 cM on mouse Chromosome 7 and is linked to anti-ovarian autoantibodies at D7Mit340 and D7Mit77. Interaction between Aod5 and Aod3 appears to affect the oophoritis phenotype. The candidate gene for Aod5, Mater, is a known ovarian autoantigen, the sequence was compared between C57BL/6J and A/J. Four splice variants of Mater were observed in A/J and two splice variants were observed in C57BL/6J. One of the splice variants results in a 3 amino acid difference between C57BL/6J and A/J.

References

• Original: J:78005 Roper RJ, et al., Interacting quantitative trait loci control loss of peripheral tolerance and susceptibility to autoimmune ovarian dysgenesis after day 3 thymectomy in mice. J Immunol. 2002 Aug 1;169(3):1640-6
• All: 1 reference(s)