PMC

Effect of the Chr7 on the course of tuberculosis following low dose aerosol challenge with M. tuberculosis Erdman. A: Bacterial loads in organs of C3H.B6-sst1 and C3H.B6-sst1,Chr7^B6 mice at 2, 6, 12 and 20 weeks post aerosol challenge with 30 -50 CFU of MTB strain Erdman. Four mice per strain were sacrificed at each time point. B: Tuberculosis lung lesion histopathology of the C3H.B6-sst1 and C3H.B6-sst1,Chr7^B6 mice 20 weeks following low dose aerosol infection with MTB. Upper panels – H&E, original magnification 200×, lower panels – auramine-rhodamine staining of acid fast mycobacteria, original magnification 400×.

The Chr7 locus mapping using Chr7 interval-specific subcongenic mouse strains.
A: Schematic diagram of the chromosome 7 interval-specific subcongenic mouse strains. Black and white boxes represent homozygous C57BL/6J and C3HeB/FeJ-derived alleles respectively. The chromosome 7 subcongenic strains mouse strains A, B, C, D are sst1^R. The Chr7 allele is determined based on survival (panels B and C) and organ bacterial loads (panel D) after i.v. infection with MTB. B: Survival of four chromosome 7 subcongenic mouse strains A, B, C and D and the parental C3H.B6-sst1 and C3H.B6-sst1,Chr7_B6 mice after i.v. infection with a standard dose of MTB Erdman. C: Pairwise comparisons of survival curves of each subcongenic strain with the parental strains to determine allele of the Chr7 locus. D: Bacterial burdens in the organs of the Chr7 subcongenic and parental mouse strains 10 weeks post infection with 5 × 10₄ CFU of MTB i.v.

Effect of the Chr7 locus on the course of tuberculosis in C3HeB/FeJ genetic background mice. A: Left panel Survival of the parental C3HeB/FeJ and Chr7 consomic strain (C3H-Chr7^B6) following systemic i.v. challenge with 4 × 10⁴ CFU of M. tuberculosis Erdman. Right panel Survival of parental C3HeB/FeJ (C3H) and C3H-Chr7^B6 consomic mice following aerosol challenge with 30 - 50 CFU of M. tuberculosis Erdman. Six to eight mice per group were used in each experiment. B: Interactions of the Chr7 and sst1 loci during the course of tuberculosis following i.v. challenge with M. tuberculosis Erdman. MTB burden (CFU) in the organs of the C3H–Chr7^B6 (sst1^S, S) and C3H.B6-sst1, Chr7B6 (sst1^R, R) at 45 days post i.v. challenge with 5×10⁴ CFU of MTB (four mice per group).C: Histopathology of representative tuberculosis lung lesions of the C3H-Chr7^B6 left panel and C3H.B6-sst1,Chr7^B6 right panel double congenic mice 45 days post i.v. challenge (H&E, original magnification 40×). H&E, original magnification 40×; inset acid fast fluorescent staining of MTB, original magnification 400×.

The Chr7 effect on the course of tuberculosis in the sst1^R genetic background following i.v. challenge with M. tuberculosis Erdman. A: Dose-dependent effect of the B6-derived resistance allele of the Chr7 locus on survival of the sst1^R mice after systemic i.v. infection with 7 × 10⁴ CFU of MTB. All mice in this experiment are homozygous for the susceptible allele of the Chr7 locus. The C3H.B6-sst1,chr7^bh and C3H.B6-sst1,chr7^bb carry one or two B6-derived resistant alleles of Chr7, respectively. Seven to twelve mice per group were used in the experiment. B: Tuberculosis lung lesion histopathology in the sst1^R congenic mouse strains C3H.B6-sst1 and double congenic C3H.B6-sst1,Chr7^B6 56 days post infection with MTB (H&E, original magnification 40×). C: Kinetic analysis of mycobacterial loads in spleens, lungs and livers of the parental C57BL/6 (B6), C3H.B6-sst1 and C3H.B6-sst1, chr7^B6 mice 18, 38 and 56 days post i.v. challenge with5 × 10⁴ CFU of MTB.