Tnbs1^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Tnbs1^C57BL/6J
• Name: tri-nitrobenzene sulfonic acid susceptible 1; C57BL/6J
• MGI ID: MGI:3033600
• QTL: Tnbs1 Location: Chr9:85779563-87826225 bp Genetic Position: Chr9, cM position of peak correlated region/allele: 46.41 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL

Notes

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

J:82169

Tri-nitrobenzene sulfonic acid (TNBS) can induce colitis in SJL/J but not in C57BL/6J. Crosses involving SJL/J and C57BL/6J were informative in mapping two QTLs to mouse Chromosomes 9 and 11. The Chromosome 9 QTL mapped with D9Mit196 and the Chromosome 11 QTL mapped with D11Mit186.

J:82095

Linkage analysis was performed on 385 (C57BL/6J x SJL/J)F2 animals to identify QTL associated with tri-nitrobenzene sulfonic acid (TNBS)-induced colitis. Colitis was induced by rectal administration of a TNBS-ethanol solution and animals were followed for 4 days after induction. Parental strain C57BL/6J is resistant to TNBS-induced colitis whereas parental strain SJL/J is highly susceptible (diarrhea, severe weight loss, and histopathological changes in the colon). 118 polymorphic markers at an average spacing of 13 cM were used for the genome scan.

Significant linkage to colitis susceptibility mapped to mouse Chromosome 9 between D9Mit269 (43 cM) and D9Mit196 (48 cM) with LOD=5.1. This locus is named Tnbs1 (tri-nitrobenzene sulfonic acid susceptible 1). The effect of Tnbs1 is highly significant in males and weakly significant in females. SJL/J-derived alleles at Tnbs1 confer colitis susceptibility. Ibdq1 (34 cM), a previously identified QTL linked to inflammatory bowel disease named maps near Tnbs1.

Significant linkage to colitis susceptibility in female animals mapped to mouse Chromosome 11 between D11Mit151 (13 cM) and D11Mit186 (17 cM) with LOD=5.5. This locus is named Tnbs2 (tri-nitrobenzene sulfonic acid susceptible 2). SJL/J-derived alleles at Tnbs2 confer colitis susceptibility. A potential candidate gene mapping to the Tnbs2 locus is Il12b (19 cM). SJL/J animals exhibit significantly increased Il12b expression after LPS injection compared to C57BL/6J animals. In addition, F2 animals injected with LPS exhibit a higher IL12b response in females compared to males. The genomes of C57BL/10J and C57BL/6J are 99% homologous yet C57BL/10J is susceptible to TNBS-induced colitis. These 2 strains differ on chromosome 11 from D11Mit110 (17.6 cM) to D11Mit111 (25 cM), which overlaps Tnbs2. C57BL/10J animals also exhibit increased Il12b response to LPS compared to C57BL/6J animals. Previously identified autoimmunity QTL mapping near Tnbs2 are Eae6a (7 cM) and Eae6b (24 cM). Tnbs2 is syntenic to a region on human Chromosome 5q33-q34 associated with Crohn's disease.

References

• Original: J:82169 Bouma G, Mapping of QTLs Tnbs1 and Tnbs2 to mouse Chromosomes 9 and 11 respectively. MGI Direct Data Submission. 2003
• All: 2 reference(s)