Tbrs4^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Tbrs4^C57BL/6J
• Name: tuberculosis resistance 4; C57BL/6J
• MGI ID: MGI:2664018
• Synonyms: Trl-4
• QTL: Tbrs4 Location: unknown Genetic Position: Chr19, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers resistance to infection by Mycobacterium tuberculosis compared to DBA/2J. (J:83619)
• Inheritance: Semidominant

Notes

Homozygosity for C57BL/6J-derived alleles at both Tbrs3 and Tbrs4 confers complete resistance to infection by Mycobacterium tuberculosis.

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

J:83619

151 microsatellite markers at an average resolution of 10 cM were screened in 98 (C57BL/6J x DBA/2J)F2 animals to identify loci affecting Mycobaterium tuberculosis infection. Parental strain C57BL/6J is resistant to M. tuberculosis infection compared to DBA/2J.

A QTL with significant linkage to tuberculosis resistance, Tbrs4, mapped to an interval spanning 47 cM - 52 cM on mouse Chromosome 19 with a peak LOD score = 5.59 at D19Mit54 and D19Mit103. C57BL/6J-derived alleles confer decreased bacterial replication with incomplete dominance at this locus. Tbrs4 maps to the same region as another inflammatory response QTL, Pgia12. Potential candidate genes for Tbrs4 include Chuk, Nfkb2, and Csf2ra.

Suggestive QTLs mapped to 34 cM (D5Mit254, LOD=3.78) and 72cM (D5Mit216, LOD=3.42) on mouse Chromosome 5, 18 cM (D7Mit270, LOD=3.14) on mouse Chromosome 7, and to 29 cM (D10Mit194, LOD=3.4) on mouse Chromosome 10. These loci did not reach genome-wide significance.

Tbrs4 shows strong interaction with Tbrs3 on mouse Chromosome 7 (LOD = 10.09). Homozygosity for C57BL/6J-derived alleles at both Tbrs4 and Tbrs3 confer complete resistance to infection by M. tuberculosis.

References

• Original: J:83619 Mitsos LM, et al., Susceptibility to tuberculosis: a locus on mouse chromosome 19 (Trl-4) regulates Mycobacterium tuberculosis replication in the lungs. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6610-5
• All: 1 reference(s)