Disease relevance of Yaa

• The BXSB Y chromosome-linked mutant gene, Yaa, promotes autoimmune responses in mice predisposed to a lupus-like autoimmune disease [1].
• The Yaa gene-mediated acceleration of murine lupus: Yaa- T cells from non-autoimmune mice collaborate with Yaa+ B cells to produce lupus autoantibodies in vivo [1].
• Autoimmune accelerating genes, lpr and Yaa, in murine systemic lupus erythematosus [2].
• Yaa mice ameliorated nephritis, and suppressed production of autoantibodies and the accumulation of abnormal T cells [3].
• Yaa mice spontaneously developed a massive lymphadenopathy characterized by hypergammaglobulinemia, the presence of several autoantibodies, and autoimmune disease [3].

Psychiatry related information on Yaa

• BXSB/ MpJ-Yaa and NZB/BINJ mice have been used as animal models for both developmental learning disability and systemic autoimmune disease [4].

High impact information on Yaa

• Yaa modifies the specificity and thus the pathogenicity of the B6 [5].
• Males from the BXSB murine strain (H-2b) spontaneously develop an autoimmune syndrome with features of systemic lupus erythematosus (SLE), which results in part from the action of a mutant gene (Yaa) located on the Y chromosome [6].
• We compared the clinical development (autoantibody production and glomerulonephritis) of systemic lupus erythematosus (SLE) in these three F1 hybrids in the presence or absence of the mutant gene, Yaa (Y chromosome-linked autoimmune acceleration), which normally accelerates the progression of murine SLE [7].
• The Yaa gene abrogates the major histocompatibility complex association of murine lupus in (NZB x BXSB)F1 hybrid mice [7].
• It contains 212 base pairs of sequence coding for (Gly-Xaa-Yaa)n (where Xaa and Yaa are different unspecified amino acids), characteristic of all known collagen genes [8].

Chemical compound and disease context of Yaa

• GATA-3 overexpression in T cells improved the 50% mortality incidence time for GATA-3-transgenic Yaa mice (41.6 wk), compared with Yaa mice (30.9 wk), and reduced proteinuria, serum creatinine levels, and the severity of glomerulonephritis in GATA-3-transgenic Yaa mice [9].

Biological context of Yaa

• Unlike the lpr gene, which causes the defects in the Fas antigen-mediating apoptosis, the autoimmune enhancing activity of the Yaa gene is selective, depending on autoantigens, and varies among lupus-prone mice [10].
• A mutant gene located on the BXSB Y chromosome, designated Yaa (Y chromosome-linked autoimmune acceleration), is responsible for the acceleration of the disease observed in male BXSB mice [11].
• This suggests that the molecular defect of the Yaa gene is likely to differ from that of the lpr gene, and that the Yaa gene effect requires the abnormal autosomal genome present in lupus-prone mice [11].
• Linkage of a major quantitative trait locus to Yaa gene-induced lupus-like nephritis in (NZW x C57BL/6)F1 mice [12].
• To investigate whether the H-2b haplotype and/or the lack of expression of I-E molecules play any role in the Yaa-linked acceleration of autoimmune disease, an I-E+ BXSB.H-2d congenic strain was created by backcross procedures [13].

Anatomical context of Yaa

• We have previously shown that a cognate interaction of T cells with B cells expressing the Yaa gene appears to be responsible for the accelerated production of autoantibodies [1].
• We then determined autoantibody production following the selective elimination of T cells of Yaa+ origin by treating mice with allele-specific anti-Thy-1 monoclonal antibody [1].
• Moreover, studies on Yaa(+)-Yaa- double bone marrow chimeric mice revealed that B cells from Yaa+ mice were selectively stimulated to produce antibodies to low-responding antigen, human IgG, while both B cell populations similarly responded to high-responding antigen, ovalbumin [10].
• Thus, the selective immune enhancing activity of the Yaa gene may be related to differences in the capacity of T helper cells specific for given antigens [11].
• Cell electrophoretic characterization of abnormally expanded lymphocytes in autoimmune lprcg, lpr, gld and Yaa mice, and of thymocyte subsets [14].

Associations of Yaa with chemical compounds

• Yaa mice and the suppressive effect of cyclophosphamide (CP) on the mice [3].
• Two further interruptions of the triple helix were indicated by single deletions of GLy or Yaa positions in the triplet structure (Gly-Xaa-Yaa)n. The two 3-hydroxyproline residues were found in position Xaa and are surrounded by homologous sequences [15].
• The distribution of amino acids between the Xaa and Yaa position was similar to that found in interstitial collagens but the extent of proline and lysine hydroxylation differed [16].
• The tetrapeptide sequence Boc-Tyr(tBu)-D-Xaa-Phe-Yaa-OH (Xaa = Lys, Orn, A2bu; Yaa = Pro in L- or D-configuration) was used to study the influence of ring size and chirality on the yield of cyclization between the omega-amino group of Xaa and the C-terminal carboxyl group [17].

Regulatory relationships of Yaa

• Although IL-4 production remained unchanged, intracellular cytokine analyses demonstrated that IL-5 was induced and IFN-gamma was suppressed in stimulated T cells from the GATA-3-transgenic Yaa mice [9].
• Marked acceleration of the autoimmune disease in MRL-lpr/lpr mice by the influence of the Yaa gene from BXSB mice [18].

Other interactions of Yaa

• We have used congenic strains to analyze the interactions between the Sle1 subloci and other lupus susceptibility loci using Y autoimmunity accelerator (Yaa) and Faslpr as sensitizing mutations [19].
• We studied NZB, MRL/lpr, BXSB/Yaa, C3H/gld mice and BALB/c and C57BL/6 as control mice [20].
• The xid and Yaa mutations had minimal effects on expression of 8.4-kb MCF-related transcripts, despite their major and opposite effects on disease [21].
• Yaa mice developed autoimmune nephritis similarly to BXSB/MpJ-Yaa mice, which are commonly used as a model for Th1-dominant murine lupus [9].
• These results indicated that abundant GATA-3 was unable to stimulate complete differentiation of Th2 cells but did counteract the dominance of Th1 cells and alleviated the disease severity in Yaa mice [9].

Analytical, diagnostic and therapeutic context of Yaa

• By using MTS33, MTS35 and flow cytometry, both C3H/gld and BXSB/Yaa, but not MRL/lpr mice, showed decreased cortical thymocyte frequencies [22].
• Effects of embryo transfer and cortical ectopias upon the behavior of BXSB-Yaa and BXSB-Yaa + mice [23].

References