Mtv7^DBA/2
QTL Variant Detail

Summary

• QTL variant: Mtv7^DBA/2
• Name: mammary tumor virus locus 7; DBA/2
• MGI ID: MGI:3696551
• Synonyms: Mls-1^a
• QTL: Mtv7 Location: unknown Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: DBA/2

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers resistance to collagen-induced arthritis compared to BALB/c, B10.RIII, and B10.Q. (J:27701)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

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

J:52834

64 polymorphic markers were typed in a population of (B10.D2-H2^d x DBA/2J)F1 x B10.D2-H2^d backcross mice and (B10.D2-H2^d x DBA/2J)F1 x DBA/2J backcross mice to identify QTLs associated with graft-versus-host disease (B10=C57BL/10J; D2=DBA/2J). Spleen cell from backcross animals were intraperitoneally injected into (C57BL/10J x DBA/2J)F1 recipients to induce graft-versus-host disease, and splenomegaly was measured as an indicator of disease. F1 animals receiving spleen cells from (B10.D2-H2^d x DBA/2J)F1 x B10.D2-H2^d backcross donors showed higher incidence of graft-versus-host disease than F1 animals receiving spleen cells from (B10.D2-H2^d x DBA/2J)F1 x DBA/2J backcross donors. Donor animals homozygous for C57BL/10J-derived alleles appear to induce more severe disease in F1 recipients. QTL analysis revealed a major locus on distal mouse chromosome 1 segregating with this trait. This locus, Gvhd1 (graft-versus-host disease 1), maps to 78 cM - 112 cM on mouse chromosome 1 yielding a peak LOD score = 27 at D1Mit150. Candidate genes near the region of Gvhd1 are Cd48 and Mtv7. A second locus, Gvhd2, mapped to approximately 76 cM - 81 cM on mouse chromosome 4 yielding a peak LOD score = 7.2 near D4Mit42. A candidate gene in the region of Gvhd2 is Tnfrsf8 (Cd30). Animals homozygous for C57BL/10J-derived alleles at both Gvhd1 and Gvhd2 induced the most severe disease response in F1 recipients. A suggestive locus mapped to mouse chromosome 6 near D6Mit86 (P<0.02).

J:58134

The B6.D2-Mtv7^a/J congenic line was used to verify Cplaq3. This congenic carries DBA/2J-derived DNA at the Mtv7 locus (between 89 cM and 106 cM) on a C57BL/6J genetic background. The congenic region includes Cplaq3 (94.2 cM) and contains DBA/2J-derivedDNA from D1Mit206 to D1Mit273. Parental strain C57BL/6J exhibits greater locomotor activity during the circadian period (longer tauDBX) compared to parental strain DBA/2J (shorter tauDBX). The B6.D2-Mtv7^a/J congenic exhibits decreased circadian locomotor activity compared to the background strain C57BL/6J thus confirming the decreasing effect of DBA/2J-derived alleles.

03.11.2015 Curator Note: Because Cplaq3 was originally mapped in J:36675 in 1995 uisng 13 CXB (BALB/cBy x C57BL/6By) recombinant inbred strains, which differ from the congenic mice used here, we consider the currant study a separate mapping experiment and have named the QTL identified Cplaq13.

Candidate genes found near Cplaq3 are Nhlh1, Kcnj10, Pou2f1, Ddr2, Lmx1a, Vangl2, Atp1b1, Mop3, and Rxrg.

J:41574

Malaria resistance mapped near the Mtv7 locus (96 cM) on mouse Chromosome 1 in BALB.D2-Mtv7 congenic animals. Background strain BALB/c is susceptible to infection with Plasmodium yoelii and develops severe anemia and a high degree of parasitemia whereas the congenic BALB.D2-Mtv7 is resistant (mild anemia and low degree of parasitemia). The malaria resistance locus, designated Mlrrq (malaria resistance QTL) is linked to but independent of Mtv7.

Mtv7 results in deletion of T cells bearing Vbeta6, 7, 8.1,and 9 T cell receptor elements. Neonatal BALB/c (susceptible) animals given 10⁸ BALB.D2-Mtv7 spleen cells within 24 hours after birth did not exhibit increased resistance to P. yoelli. In addition, athymic nude mice given T cells from BALB/c or BALB.D2-Mtv7 animals did not display differences in the course of infection. Therefore, the data suggests the Mtv7 locus is not involved in P. yoelli resistance, but a nearby linked gene, Mlrrq, is responsible for the effect. Spna1 at 95.4 cM is a potential candidate gene for Mlrrq.

References

• Original: J:27701 Anderson GD, et al., Role of Mls-1 locus and clonal deletion of T cells in susceptibility to collagen-induced arthritis in mice. J Immunol. 1991 Aug 15;147(4):1189-93
• All: 3 reference(s)