Tilss3^DBA/2NCrl
QTL Variant Detail

Summary

• QTL variant: Tilss3^DBA/2NCrl
• Name: TNF-induced lethal shock susceptibility 3; DBA/2NCrl
• MGI ID: MGI:3713357
• QTL: Tilss3 Location: unknown Genetic Position: Chr17, cM position of peak correlated region/allele: 55.02 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: DBA/2NCrl

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers resistance to TNF-induced lethal shock compared to C57BL/6JIco. (J:122128)
• Inheritance: Recessive

Notes

The recessive nature of this allele was not apparent in the initial intercross and backcross study.

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

J:122128

Linkage analysis was performed on 100 females from a (C57BL/6JIco x DBA/2NCrl)F1 x C57BL/6JIco backcross and 90 female animals from a (C57BL/6JIco x DBA/2NCrl)F2 intercross to identify QTLs associated with TNF-induced lethal shock. A panel of 69 microsatellite markers was used for genome scan. Animals were injected with 75 ug TNF at 8-12 weeks of age and scored over 5 days. C57BL/6JIco exhibits high TNF sensitivity with almost all animals dying at a 20 ug dose, whereas DBA/2NCrl and (C57BL/6JIco x DBA/2NCrl)F1 animals survive up to 100 ug doses.

A major resistance locus mapped to 51 cM on mouse Chromosome 6 near D6Mit150 (LRS=18.1). This locus was confirmed using a chromosome substitution line at generation N9 carrying a DBA/2NCrl-derived donor chr 6 ona C57BL/6JIco genetic background (C57BL/6JIco-Chr 6^DBA/2NCrl). Homozygous and heterozygous C57BL/6JIco-Chr 6^DBA/2NCrl animals were significantly more resistant to TNF-induced lethal shock compared to C57BL/6JIco controls, but were not as resistant asDBA/2NCrl. In addition, tumor-bearing homozygous C57BL/6JIco-Chr 6^DBA/2NCrl animals can withstand a 10-day treatment of TNF/INF-gamma resulting in complete tumor remission. Subcongenic line analysis narrowed the QTL interval to a 13.2 Mb region betweenD6Mit54 (48.2 cM, 113.2 Mb) and D6Mit254 (60.55 cM, 126.2 Mb). This locus colocalizes with Tilss1 (45 cM), a TNF resistance QTL previously identified by the same authors. Potential candidate genes identified by SNP analysis and include Alox5 (53.2 cM), A2m (61.7 cM), and Tnfrsf1a (60.55 cM).

04.13.2015 Curators Note: Because Tilss1 was orginally mapped in J:77727 in 2003 using a (C57BL/6 x SPRET/Ei)F1 x C57BL/6 backcross, which differs from the cross used here, we consider this a sparate map study and have named the QTL Tilss4.

A second resistance locus mapped to 53 cM on mouse Chromosome 17 near D17Mit41 (LRS=7) and was confirmed in the C57BL/6JIco-Chr 17^DBA/2NCrl chromosome substitution (CS) line. However, only homozygous CS animals displayed resistance to TNF-induced lethal shock indicating this locus exhibits a recessive effect. This QTL is designated Tilss3 (TNF-induced lethal shock susceptibility 3).

References

• Original: J:122128 Wielockx B, et al., Description and mapping of the resistance of DBA/2 mice to TNF-induced lethal shock. J Immunol. 2007 Apr 15;178(8):5069-75
• All: 1 reference(s)