Tbs1^I/StSnEgYCit
QTL Variant Detail

Summary

• QTL variant: Tbs1^I/StSnEgYCit
• Name: tuberculosis severity 1; I/StSnEgYCit
• MGI ID: MGI:2155337
• QTL: Tbs1 Location: Chr3:115924105-115924250 bp Genetic Position: Chr3, cM position of peak correlated region/allele: 50.18 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: I/StSnEgYCit

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: The heterozygous state confers increased body weight loss and increased survival time in female animals infected with Mycobacterium tuberculosis.
• Inheritance: Not Specified

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

This locus affects M. tuberculosis-induced body weight loss in female animals.

This allele appears to interact with I/StYCit-derived alleles at D17Mit175 to increase neutrophil inflammation following challenge with M. tuberculosis.

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

J:55857

Mice of the inbred strains I/StSnEgYCit and A/SnYCit show significant differences in disease severity after an intravenous injection of a lethal dose of the virulent human isolate of M. tuberculosis H37Rv. Following challenge with H37Rv, only I/St mice have rapid body weight loss and short survival times. A genome wide analysis for linkage with body weight afetr injection was done in 105 [(A/Sn x I/St)F1 x I/St] backcross mice. A locus on distal Chromosome 3, Tbs1 showed significant linkage with body weight in females, with a LOD score of 3.92. A possible candidate is the Pxmp1 gene.

J:80972

Tbs1 and Tbs2 are previously mapped QTLs associated with tuberculosis suvival time. Tbs1 is located on distal mouse Chromosome 3 and Tbs2 is located at 23 cM on mouse Chromosome 9. In the present study the authors extend genotype analysis using 406 (A/SnYCit x I/StSnEgYCit)F2 animals to futher narrow the QTL region and also to investigate linkage to body weight and survival time. Parental strain I/StSnEgYCit exhibits decreased body weight and shorter survival time following infection with Mycobacterium tuberculosis compared to parental strain A/SnYCit. In addition, I/StSnEgYCit females exhibit shorter survival time than I/StSnEgYCit males.

Tbs1 was localized to a 12 cM interval centered on D3Mit215 at 55 cM on mouse Chromosome 3. Females with a heterozygous genotype at Tbs1 exhibit decreased body weight and longer survival times compared to females homozygous for either I/StSnEgYCit-derived or A/SnYCit-derived alleles. Tbs1 appears to be involved in epsitatic interactions with Tbs2 and a locus on mouse Chromosome 17.

Tbs2 was localized to a 9 cM interval centered on D9Mit89 at 8 cM on mouse Chromosome 9. Females with a heterozygous genotype at Tbs2 exhibit decreased body weight and longer survival times compared to females homozygous for either I/StSnEgYCit-derived or A/SnYCit-derived alleles. Body weight loss shows suggestive linkage in male animals, LOD=2.3. Tbs2 overlaps with the Leishmaniasis resistance QTL, Lmr2.

Suggestive linkage to body weight loss and survival time was detected on mouse Chromosome 17 at D17Mit28 (18.44 cM) for males and at D17Mit175 (17.7 cM) for females. This maps relatively close to the H2 locus. Animals homozygous for A/SnYCit-derived alleles at this locus exhibit decreased tuberculosis severity. This locus appears to interact with Tbs1. Females homozygous for A/SnYCit-derived alleles at Tbs1 and homozygous for I/StSnEgYCit-derived alleles at D17Mit175 exhibit the greatest body weight loss.

A locus at DXMit170 also appears to interact with Tbs2 and the chromosome 17 locus. Homozygosity for A/SnYCit-derived alleles at DXMit170 influences body weight loss in conjunction with Tbs2 and D17Mit28/D17Mit175.

References

• Original: J:55857 Lavebratt C, et al., Severity of tuberculosis in mice is linked to distal chromosome 3 and proximal chromosome 9. J Infect Dis. 1999 Jul;180(1):150-5
• All: 3 reference(s)