Sle18^C57BL/6
QTL Variant Detail

Summary

• QTL variant: Sle18^C57BL/6
• Name: systematic lupus erythematosus susceptibility 18; C57BL/6
• MGI ID: MGI:3531339
• QTL: Sle18 Location: Chr3:87208904-125316236 bp Genetic Position: Chr3, Syntenic

Variant origin

• Strain of Specimen: C57BL/6

Variant description

• Allele Type: QTL
• Inheritance: Recessive

Notes

Sle16 and Sle18 interact. F2 animals with at least one 129-derived allele at Sle16 and homozygous for C57BL/6-derived alleles at Sle18 display significantly greater ANA compared to other F2 genotypes.

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

J:93297

Linkage analysis was performed on 141 female animals from a (129S6/SvEvTac x C57BL/6)F2 intercross to identify QTLs associated with systemic lupus erythematosus phenotypes. (129S6/SvEvTac x C57BL/6)F1 hybrid animals develop spontaneous autoimmunity. 143 polymorphic microsatellite markers were used for the genome scan. 158 homozygous mutant female animals from a (129S6/SvEvTac x C57BL/6)F2-Apcs^tm1Mpe intercross were also evaluated separately.

Significant linkage to antinuclear antibody (ANA) production mapped to 96 cM on mouse Chromosome 1 near Tgfbm2 (formerly D1Mit17; LOD=5.4). This locus is named Sle16. Sle16 also shows strong linkage to anti-ssDNA antibody production (LOD=5.6). 129S6/SvEvTac-derived alleles confer increased ANA production and anti-ssDNA production. Previously identified lupus QTLs mapping near Sle16 are Sle1 (88 cM), Nba2 (95 cM), and Sle9/Bsx3 (100 cM). Because Sle16 maps close to the Apcs gene at 94 cM, 33 (129S6/SvEvTac x C57BL/6)F2 intercross mice homozygous for 129S6/SvEvTac-derived alleles between 80cM - 100 cM were compared to the 158 homozygous mutant (129S6/SvEvTac x C57BL/6)F2-Apcs^tm1Mpe animals. No difference in autoantibody levels was observed between the 2 groups suggesting that 129S6-derived DNA influences autoantibody phenotypes instead of a lack of Apcs genes. A congenic line was created by introgressing 129S6-derived DNA between D1Mit105 (80 cM) and D1Mit223 (106.3 cM) onto a C57BL/6 genetic background. Congenic animals display increased autoantibody production.

Significant linkage to anti-ssDNA antibody production mapped to 50 cM - 60 cM on mouse Chromosome 1 between D1Mit123 (21 cM) and D1Mit139 (65 cM) (LOD=3.9). This locus is named Sle17. 129S6-derived alleles confer increased anti-ssDNAproduction. Sle17 was also detected in the (129S6/SvEvTac x C57BL/6)F2-Apcs^tm1Mpe intercross population although with suggestive significance (LOD=2.9).

Highly significant linkage to SLE susceptibility mapped to 51 cM on mouse Chromosome 3 between D3Mit40(39.7 cM) and D3Mit13 (61.8 cM). This locus is named Sle18. Sle18 contributes to ANA production (LOD=5.4) and shows weaker association to anti-ssDNA (LOD=1.9) and anti-chromatin antibody production (LOD=1.8). C57BL/6-derived alleles confer increased production of ANA, anti-ssDNA and anti-chromatin antibodies. Linkage analysis was performed while controlling for Sle16 on Chromosome 1 and the LOD score increased from LOD=5.4 to LOD=6.4. Sle18 was also detected in the (129S6/SvEvTac x C57BL/6)F2-Apcs^tm1Mpeintercross populationwith LOD=1.8.

Suggestive linkageto anti-dsDNA antibody production mapped to mouse Chromosome 1 at 17 cM (LOD=2.2 between D1Mit3 and D1Mit213), 77 cM (LOD=3.2 between D1Mit139 and D1Mit105), and 92 cM. The locus at 17 cM was also detected in the (129S6/SvEvTac x C57BL/6)F2-Apcs^tm1Mpe intercross population with LOD=2.9.

Suggestive linkage to anti-chromatin antibody production mapped to 88 cM on mouse Chromosome 1 (LOD=3.0 between D1Mit83 and D1Mit115) and to 35 cM on mouse Chromosome3 (LOD=1.8 atD3Mit278). The chromsome 3 locus was also detected in the (129S6/SvEvTac x C57BL/6)F2-Apcs^tm1Mpe intercross population with LOD=2.4.

Suggestive linkage to glomerulonephritis mapped to mouse Chromosome 7 between D7Mit246 (15 cM) and D7Mit145 (26.5 cM) (LOD=2.86) and to mouse Chromosome 17 between D17Mit100 (11.7 cM) andD17Mit216 (29.4 cM) (LOD=1.3).

References

• Original: J:93297 Bygrave AE, et al., Spontaneous autoimmunity in 129 and C57BL/6 mice-implications for autoimmunity described in gene-targeted mice. PLoS Biol. 2004 Sep;2(8):E243
• All: 2 reference(s)