Kif1c^Orch3-DBA/2J
QTL Variant Detail

Summary

• QTL variant: Kif1c^Orch3-DBA/2J
• Name: kinesin family member 1C; DBA/2J
• MGI ID: MGI:3036096
• QTL: Kif1c Location: Chr11:70591374-70622790 bp, + strand Genetic Position: Chr11, 43.21 cM

Variant origin

• Strain of Specimen: DBA/2J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: Mapping experiments restricted the QTL region to a restricted region in which Kif1c is the most likely candidate gene for the experimental autoimmune orchitis trait. Further, insertion of a transgene containing the resistance allele of this QTL to the susceptible background reduced susceptibility. This allele confers orchitis resistance compared to BALB/cByJ. (J:35331)
• Inheritance: Dominant

Notes

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

J:103336

The anthrax lethal toxin susceptibility locus Kif1c^Ltxs1 (42 cM, chr11) was further characterized using interval-specific recombinant congenic strains (ISRC). ISRC lines carrying different DBA/2NCr-derived portions of central mouse Chromosome 11 on a BALB/cAnPt genetic background were constructed. The progenitor strain DBA/2NCr is resistant to anthrax lethal toxin whereas progenitor strain BALB/cAnPt is susceptible. ISRC animals were injected intravenously with anthrax lethal toxin at 6- to 12-weeks ofage.

The DBA/2NCr allele of Kif1c^Ltxs1 was found to confer partial resistance to anthrax lethal toxin. Two additional resistance loci linked to Kif1c on mouse Chromosome 11 were identified in this study. Ltxs2 (lethal factor toxin susceptibility 2) maps proximal to Kif1c between D11Mit88 (34.5 cM) and D11Mit4 (37 cM). Ltxs3 (lethal factor toxin susceptibility 3) maps distal to Kif1c between D11Bhm149 (44.7 cM) and D11Bhm169 (46.5 cM). DBA/2NCr resistance alleles at Kif1c^Ltxs1, Ltxs2, and Ltxs3 confer partial resistance to anthrax lethal toxin when acting separately, but DBA/2NCr resistance alleles at all three loci will reconstitute full resistance. Both Ltxs2 and Ltxs3 exhibit dominant resistance to anthrax lethal toxin.

An attractive candidate gene for Ltxs3 is Nos2 (45.6 cM). Lethal factor is known to inhibit NO production in macrophages and Nos2 knockout mice die sooner from anthrax infection compared to wild type mice. Nos2 macrophage expression also differs significantly between BALB/c and DBA/2 as determined by RT-PCR.

References

• Original: J:35331 Meeker ND, et al., Multiple loci govern the bone marrow-derived immunoregulatory mechanism controlling dominant resistance to autoimmune orchitis. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5684-8
• All: 2 reference(s)