Pgia35^DBA/2Crl
QTL Variant Detail

Summary

• QTL variant: Pgia35^DBA/2Crl
• Name: proteoglycan induced arthritis 35; DBA/2Crl
• MGI ID: MGI:5661395
• QTL: Pgia35 Location: Chr4:29562377-29562509 bp Genetic Position: Chr4, Syntenic

Variant origin

• Strain of Specimen: DBA/2Crl

Variant description

• Allele Type: QTL

Notes

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

J:84150

Linkage analysis was performed on 559 proteoglycan-immunized (BALB/cCrl x DBA/2Crl)F2 animals to detect QTLs associated with arthritis susceptibility, severity, and onset. BALB/cCrl females are 100% susceptible to proteoglycan-induced arthritis (PGIA) whereas DBA/2Crl males are resistant. F1 hybrid males and females are also resistant to PGIA.

Several previously identified PGIA loci were confirmed in this study. These include Pgia1, Pgia4, Pgia6, Pgia7 Pgia8, Pgia9, Pgia12.

The authors cite the following marker as having been previously mapped; however, differing parental strains were used in the previous map studies. We have renamed the QTL as follows:

The authors refer to Pgia13 on mouse chromosome 4. This QTL was originally mapped using an

(C57BL/6x C3H/HeJCr)F2 intercross. We have renamed the QTL Pgia35, mapped here using (BALB/cCrl x DBA/2Crl)F2 mice. This QTL maps to mouse chromosome 4 at D4Mit97 with LOD=3.1 for arthritis severity in male mice. The Pgia35 interval spanned 0-20cM on mouse chr 4.

Authors identify novel PGIA loci:

Pgia26 mapped to 52.5 cM on mouse Chromosome 3 with LOD=4.9 at D3Mit158 for arthritis onset in female animals. The Pgia26 QTL interval spans 34 cM - 80 cM on chromosome 3. BALB/cCrl-derived alleles confer high arthritis onset with codominant inheritance at Pgia26.

Pgia27 mapped to 42.5 cM on mouse Chromosome 4 with LOD=3.1 at D4Mit45 for arthritis severity in male animals. The Pgia27 QTL interval spans 35 - 45 cM on chromosome 4.

Pgia28 mapped to 14 cM on mouse Chromosome 11 with LOD=2.8atD11Mit229 for hetero antibody production in male animals. The Pgia28 QTL range spans 0 cM - 28 cM on chromosome 11.

Pgia29 mapped to 45 cM on mouse Chromosome 14 with LOD=2.8 forarthritis severity in male animals andLOD=3.5 forT cell proliferationinfemale animals at D14Mit92. The Pgia29 QTL range spans 40 cM - 54 cM on chromosome 14.

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 arefullyresistant. 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 this is not 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.

Pgia35 mapped to proximal mouse Chromosome 4 in association with PGIA severity (LOD=3) in the MHC-matched (BALB/c x DBA/2)F2 population.

References

• Original: J:84150 Adarichev VA, et al., Sex effect on clinical and immunologic quantitative trait loci in a murine model of rheumatoid arthritis. Arthritis Rheum. 2003 Jun;48(6):1708-20
• All: 2 reference(s)