Disease relevance of Mtv6

• Yet, a slightly reduced level of V beta 5+ T cells is observed in HII animals which might correlate with the presence of Mtv-6 and Mtv-9 proviruses [1].

High impact information on Mtv6

• Here we demonstrate that a second endogenous superantigen, responsible for the deletion of V beta 5-bearing T cells, is encoded by a gene mapping to Mtv-6 on chromosome 16 [2].
• Surprisingly, the carboxyl-terminal sequences of the Mtv-6 and -9 superantigens are extremely divergent, in spite of the fact that they both mediate the deletion of V beta 5+ lymphocytes [2].
• In contrast a striking pattern of differential expression was observed in dendritic cells of thymic origin that were devoid of Mtv-8/9 but expressed readily detectable levels of Mtv-6 [3].
• TCRV beta 3+ T cells, normally deleted in response to Mtv-6, were virtually absent from the single positive thymocyte compartment in thymic organ cultures where dendritic cells are present but were present in reaggregate cultures where the only MHC class II-positive cells were thymic epithelial cells [3].
• Although Mtv-6 and Mtv-8/9 mRNAs are expressed in normal thymus lobe organ cultures, no Mtv expression was detected in MHC class II+ thymic epithelial cells [3].

Biological context of Mtv6

• By interspecific backcross analysis the gene encoding BERF-1 was localized 4.7 cM proximal to the Mtv6 locus on mouse chromosome 16, and an isolated pseudogene was localized to mouse chromosome 8, about 5.3 cM distal to the D8Mit4 marker [4].
• Comparison with known open reading frame (orf) sequences revealed high homology to Mtv-6, an endogenous virus interacting with V beta 3-expressing T cells [5].
• The Mtv-6 provirus has an incomplete genome, but retains a functional superantigen gene (sag) which directs the thymic deletion of CD4+ T cells expressing T cell receptors containing the V beta 3 or V beta 5 chains [6].
• Apoptosis of TCR-V beta 3 + thymocytes caused by Mtv-6, quantified according to the down-regulation of CD4 and CD8 on immature thymocytes, was partially inhibited by CsA, to maximal effect within 24 hours [7].

Anatomical context of Mtv6

• Studies of the progeny of a B10.BR x (C3H/HeJ x B10.BR)F1 backcross confirmed the existence of two V beta 3+ T cell deleting genes: one unlinked and one linked to Ly-7, which we propose be called Mls-2 and Mls-3, respectively [8].
• In B cells as well as T cells (CD4+ or CD8+), Mtv-6 SAg is expressed at the highest levels, followed by Mtv-7 SAg and (to a much lesser extent) Mtv-8,9 [9].

Associations of Mtv6 with chemical compounds

• This factor is activated by Mtv-6 integration and mediates androgen effects in these cells [10].

Other interactions of Mtv6

• Mtv-6+ and Mtv-7+ animals deleted TcR V beta 3+ and V beta 5+ cells, and TcR V beta 6+, V beta 7+ and V beta 8.1+ cells, respectively [11].
• SM/J contains the previously described loci Mtv-6 and Mtv-8 [12].
• Genes encoding endogenous superantigens causing Tcrb-V3+ T-cell deletion co-segregate with mouse mammary tumor proviruses (Mtv), Mtv-3, Mtv-6, and Mtv-13 [13].
• Appreciable levels of mRNA corresponding to common Mtv ORF and Mtv-6 ORF were expressed in the neonatal thymus, while little, if any, mRNA corresponding to Mtv-50 ORF was detected in the thymus at the early postnatal stage [14].
• In addition, the newly integrated Mtv-6 was localized to the DNA fragment containing the Fgf8 gene [15].

Analytical, diagnostic and therapeutic context of Mtv6

• In this study, we detected expression of spliced sag RNA from the standard promoter and from an internal U3 promoter in B-cell lines expressing endogenous Mtv-6 by RT-PCR, although expression from the standard promoter appeared to be at least 10-fold higher than that observed from the internal U3 promoter [16].
• We developed a polymerase chain reaction assay in order to study the presence of retroviral transcripts homologous to the viral superantigen gene (vSAG) of Mtv-7 and Mtv-6 in various tissues [17].
• We demonstrate by Southern blotting that the genomic DNA from DD/Sio tumors and S115 cells contains Mtv-sequences (Mtv-6 and Mtv-17) which are not found in the DNA from spleen or liver of the DD/Sio mice [15].

References