Artmd1^MRL/MpJ
QTL Variant Detail

Summary

• QTL variant: Artmd1^MRL/MpJ
• Name: arthropathy in MRL and DBA/1 mice 1; MRL/MpJ
• MGI ID: MGI:3588388
• QTL: Artmd1 Location: unknown Genetic Position: Chr10, cM position of peak correlated region/allele: 37.15 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: MRL/MpJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers arthopathy susceptibility compared to DBA/1Crlj. (J:97911)
• Inheritance: Other (see notes)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Artmd1 exhibits additive inheritance.

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

J:97911

Linkage analysis was performed on 271 male animals from a (MRL/MpJ x DBA/1Crlj)F2 intercross to identify QTL associated with susceptibility to arthropathy. 107 polymorphic markers at an average spacing of 10-20 cM were used for the genome scan. Arthropathy (swelling, redness, and ankylosis) was evaluated by examining the ankle joints of male F2 animals between 8 weeks and 40 weeks of age. At 30 weeks of age, the incidence of arthropathy in DBA/1Crlj male mice is 26.7% while male MRL/MpJ mice did not exhibit arthopathy. Onset of arthropathy in male DBA/1Crlj mice is 23 weeks of age.

Significant linkage to onset and severity of arthropathy mapped to 40 cM on mouse Chromosome 10 near D10Mit259 (LOD=5.2 for onset; LOD=7.2 for severity). This locus is named Artmd1 (arthropathy in MRL and DBA/1 mice 1). MRL/MpJ-derived alleles at Artmd1 confer arthropathy susceptibility with an additive mode of inheritance. Artmd1 maps near a previously identified sialadenitis susceptibility QTL named Asm1 (39 cM). Potential candidate genes for Artmd1 are Itgb2 (41.5 cM), Bsg (42.4 cM), and Mif (40.9 cM). A second locus on mouse Chromosome 10 peaked at 34 cM near D10Mit222 (LOD=4.9 for onset; LOD=6.2 for severity).

Significant linkage to onset and severity of arthropathy mapped to 29.5 cM on mouse Chromosome 3 near D3Mit185 (LOD=5.2 for onset; LOD=3.8 for severity). This locus is named Artmd2 (arthropathy in MRL and DBA/1 mice 2). DBA/1Crlj-derived alleles at Artmd2 confer arthropathy susceptibility with an additive mode of inheritance. Artmd2 maps near previously identified QTL Cd4ts1 (29.5 cM) and Pact1 (27 cM). Potential candidate genes for Artmd2 are Pfn2 (29.3 cM), Emv39 (30.4 cM), and Mme (29.6 cM).

Artmd1 and Artmd2 appear to interact additively. Animals with combinations of susceptibility alleles at Artmd1 and Artmd2 exhibit higher incidence of arthropathy (51%). Conversely, animals with resistance alleles at both Artmd1 (homozygous DBA/1Crlj) and Artmd2 (homozygous MRL/MpJ) exhibit the lowest incidence of arthopathy (13%).

Suggestive linkage to arthropathy susceptibility mapped to 45 cM on mouse Chromosome 13 (LOD=2.6 for severity) and to 28 cM on mouse Chromosome 17 (LOD=2.2 for onset). DBA/1Crlj-derived alleles confer susceptibility to arthropathy at both of these loci.

References

• Original: J:97911 Oishi H, et al., Accelerating effect of an MRL gene locus on the severity and onset of arthropathy in DBA/1 mice. Arthritis Rheum. 2005 Mar;52(3):959-66
• All: 1 reference(s)