Cia35^C57BL/10SnSg
QTL Variant Detail

Summary

• QTL variant: Cia35^C57BL/10SnSg
• Name: collagen induced arthritis QTL 35; C57BL/10SnSg
• MGI ID: MGI:3713895
• QTL: Cia35 Location: Chr15:81811826-81811946 bp Genetic Position: Chr15, cM position of peak correlated region/allele: 38.27 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C57BL/10SnSg

Variant description

• Allele Type: QTL

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Cia35 interacts with Cia42 on chromosome 7. Cia42 has a protective effect against CIA susceptibility.

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

J:122130

Partial advanced intercross (PAI) line analysis of Cia7 on mouse Chromosome 7 and a putative collagen-induced arthritis susceptibility locus on mouse Chromosome 15 revealed several distinct QTLs. Congenic lines BQ.D1- (D7Mit69-D7Mit371) and BQ.D1- (D15Mit13-D15Mit42) were intercrossed for 7 generations to generate PAIs. A total of 576 PAI mice were analyzed for collagen-induced arthritis. BQ.D1- (D7Mit69-D7Mit371) mice are more susceptible to CIA and BQ.D1- (D15Mit13-D15Mit42) animals display higher CIA disease scores compared to animals from the C57BL/10.Q background strain, thus confirming linkage of Cia7 and chromosome 15 to CIA susceptibility.

The chromosome 15 locus can be split into two separate sex-dependent QTLs designated Cia35 and Cia37. The female-specific locus, Cia35 (48.5 cM), is associated with CIA incidence at D15Mit118 (LOD=8.8), while the male-specific locus, Cia37 (54.5 cM), is linked to CIA incidence at D15Mit41 (LOD=5.9). When Cia35 was isolated in a subcongenic line, the QTL displays a strong effect on Ab production (both sexes), and influenced CIA in males. Isolation of Cia37 in a subcongenic line revealed a significant effect on Ab production in males.

Cia34 maps to centromeric chromosome 15 and was identified during subcongenic line analysis. This QTL confers almost complete CIA resistance in both sexes (P=0.007) and also conferred decreased anti-CII IgG production (P=0.002). Cia30 at 9.9 cM is a previously identified QTL mapping near Cia34. Cia36 was mapped between Cia35 and Cia37 during subcongenic line analysis and confers CIA resistance (both sexes), as well as decreased anti-CII IgG3 and IgG1 Ab production in males.

A locus interacting epistatically with Cia35 was detected at 37 cM near D7Mit318 (LOD=5.26). This novel locus is designated Cia41. A second interacting QTL, Cia42, was detected at 65.2 cM near D7Mit371. Homozygosity for DBA/1J-derived alleles at Cia42 protects against arthritis (decreased disease incidence) when combined with Cia35, Cia36, or Cia37 on chromosome 15.

A novel QTL named Cia38 mapped to proximal chromosome 15 near D15Mit111 (17.8 cM). Cia38 is associated with antibody (Ab) production with a stronger effect in males, and is also significantly linked to CIA onset in males. When Cia38 was isolated in a subcongenic line a strong effect on anti-CII IgG3 antibodies was observed (P=0.006). Cia32 at 17.8 cM is a previously identified QTL mapping near Cia38.

References

• Original: J:122130 Ahlqvist E, et al., Fragmentation of two quantitative trait loci controlling collagen-induced arthritis reveals a new set of interacting subloci. J Immunol. 2007 Mar 1;178(5):3084-90
• All: 1 reference(s)