Disease relevance of Mefv

• Familial Mediterranean fever (FMF) is an inherited disorder characterized by recurrent episodes of fever and inflammation [1].
• Familial Mediterranean fever (FMF) is a recessive disorder characterized by episodes of fever with serositis or synovitis [2].
• The observation of a deleterious effect of pregnancy on kidney function in amyloidosis of familial Mediterranean fever suggests that pregnancy may enhance amyloidogenesis [3].
• All groups of mice were serially followed for the appearance of IgM and IgG anti-ssDNA and anti-dsDNA antibodies, splenic CFU-B, spontaneous secretion of IgM, FMF analysis, proteinuria and survival [4].

High impact information on Mefv

• Apoptosis is impaired in macrophages from pyrin-truncation mice through an IL-1-independent pathway [1].
• Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis [1].
• Most patients with FMF carry missense mutations in the C-terminal half of the pyrin protein [1].
• By analyzing low density cells obtained at varying intervals after mitogen stimulation, FMF indicated that lymphoblasts enter the S phase of their first cell cycle beginning at 20-24 h after stimulation [5].
• FMF analyses of the separated abnormal cells showed them to be Thy-1+, Ly-1+, Ly-2-, L3T4-, Ly-5(B220)+, Ly-6+, Ly-22+, Ly-24+, sIg-, ThB-, Ia-, HSA-/+, and PC.1+ and to bind at high levels lectins that normally bind preferentially to B cells [6].

Biological context of Mefv

• Mefv is localized on mouse Chromosome (Chr) 16, region A3-B1, extending a region of synteny with human Chr 16p13 [2].
• The predicted rodent proteins have several important domains and signals found in human pyrin, including a B-box zinc finger domain, Robbins-Dingwall nuclear localization signal, and coiled-coil domain [2].
• However, perhaps because of an ancient frame-shift mutation, neither the mouse nor the rat protein has an intact C-terminal B30.2 domain, in which most FMF-associated mutations have been found in human MEFV [2].
• The characteristics of the cell population that proliferates in lymphoid tissues were evaluated by the use of a) monoclonal antibodies and FMF, and b) molecular genetic studies of Ig heavy chain genes [7].
• Quantitative measurement of Ly 9 immunofluorescence by FMF on heterozygote cells shows that Ly 9 antigen expression is co-dominant and reduced in levels relative to parental homozygote cells [8].

Anatomical context of Mefv

• Consistent with its expression in granulocytes, Mefv was detected at high levels in the primary follicles and marginal zones of the splenic white pulp [2].
• Nevertheless, like the human gene, mouse Mefv is expressed in peripheral blood granulocytes but not lymphocytes [2].
• FMF analysis and absorption typing reveals a quantitatively lower level of antigen expression on thymocytes compared with spleen or lymph node cells [8].
• Murine cortisone-resistant thymocytes were separated by staining with monoclonal anti-Lyt-2 antibody and FMF into Lyt-2- and Lyt-2+ subsets in order to analyze the nature of stimulator accessory cells required to activate each of these functionally distinct T cell subpopulations [9].
• We demonstrated the regulatory role of PRP on the oxidative burst induction of normal and relapsing inflammatory disease (Behcet's disease and familial Mediterranean fever) neutrophils and monocytes [10].

References