Cia1^BALB/c
QTL Variant Detail

Summary

• QTL variant: Cia1^BALB/c
• Name: collagen induced arthritis QTL 1; BALB/c
• MGI ID: MGI:5635491
• QTL: Cia1 Location: unknown Genetic Position: Chr17, Syntenic

Variant origin

• Strain of Specimen: BALB/c

Variant description

• Allele Type: QTL

Notes

Candidate Genes

J:81372

Microarray gene expression analysis was used to identify candidate genes for QTLs associated with collagen-induced arthritis. RNA from inflamed paws of collagen-treated mice were used in the microarray analysis and compared to RNA from normal paws. 223 genes showed a four-fold or greater expression difference between inflamed and normal paws. Nine of these genes are located near previously identified arthritis severity/susceptibility QTLs and may be considered for candidates.

For Cia1 on mouse Chromosome 17 (18.6 cM near the H2 locus) differential expression was observed for H2-Eb1 (18.66 cM) and H2-T23 (19.73 cM).

For Cia2 and Cia4 on mouse Chromosome 2 (both are located at 34 cM) differential expression was observed for Fap (36 cM) and Gcg (36 cM).

For Cia3 (48.7 cM) and Cia6 (30 cM) on mouse Chromosome 6 differential expression was observed for Raf1 (52.5 cM) and Slc6a6 (38.2 cM), respectively.

For Cia5 (40 cM) on mouse Chromosome 4 differential expression was observed for Ctsk (47.9 cM) and Cd53(50.5 cM).

For Cia8 (40.4 cM) on mouse Chromosome 10 differential expression was observed for Bsg (42.4 cM).

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

J:89536

Linkage analysis at an average resolution of 10 cM was performed on 3 separate mouse crosses to map QTLs associated with proteoglycan-induced arthritis (PGIA) and collagen-induced arthritis (CIA).

559 (BALB/c x DBA/2)F2 MHC-matched animals and 402 (BALB/c x DBA/1J)F2 MHC-unmatched animals were analyzed for linkage to PGIA.

537 (BALB/c x DBA/1J)F2 animals were analyzed for linkage to CIA. With respect to PGIA, parental strain BALB/c is highly susceptible whereas parental strains DBA/2 and DBA/1J are fullyresistant. As expected, (BALB/c x DBA/2)F1 hybrids are resistant to PGIA, but interestingly (BALB/c x DBA/1J)F1 hybrids are susceptible to PGIA. This is unusual because the BALB/c allele typically exhibits recessive susceptibility to disease, but thisisnot the case with the cross to DBA/1J.

With respect to CIA, parental strain DBA/1J is highly susceptible whereas parental strains BALB/c and DBA/2 are fully resistant. All F1s exhibited susceptibility to CIA.

Linkage to arthritis susceptibility, LOD=21.0, designated as mCia1 in Fig 3 and assigned symbol Cia1; and PGIA (LOD=6.0) were detected at the H2 locus on mouse Chromosome 17 in the (BALB/c x DBA/1J)F2 MHC-unmatched population. The PGIA locus has been mapped in previous experiments (J:78168) and is named Pgia37.

Pgia20 mapped to distal mouse Chromosome 17 in (BALB/c x DBA/1J)F2 animals (independent of MHC), and is involved in PGIA susceptibility and severity.

References

• Original: J:89536 Glant TT, et al., Disease-associated qualitative and quantitative trait loci in proteoglycan-induced arthritis and collagen-induced arthritis. Am J Med Sci. 2004 Apr;327(4):188-95
• All: 1 reference(s)