Recent reports indicate that MBP-like genes are expressed in many tissues including those of the immune system. Preliminary data from our laboratory indicates that transcripts of MBP-like genes are present in the adult mouse thymus and certain monocyte/macrophage cell lines. Using exon-specific primers cDNA from thymus was amplified and the amplified products cloned and sequenced. This verified the presence of MBP transcripts and MBP-like sequences (golli-MBP). Many of these transcripts were found in a macrophage cell line and some in a T cell line. None were found in heart cDNA. Qualitative and quantitative in differences in expression were seen when the macrophage line was cultured with LPS. In light of the preliminary findings, it is proposed to ask whether expression of the different transcripts of this gene varies between mouse strains, and whether expression varies as a function of the disease state or the presence of stimulation by inflammatory cytokines or microbial products. The findings of this study might provide new clues as to the development of autoimmunity to self antigens such as myelin basic protein. Thus, the overall goal of this research project is to investigate the expression of MBP-like molecules in the immune system of selected inbred strains of mice. Included in these strains are both EAE-susceptible and resistant strains of mice. Specifically, it is proposed to 1) to characterize transcripts of MBP and MBP-like molecules qualitatively and quantitatively in the CNS and thymus of neonatal and adult SJL/J, PL/J, (SJL x PL)F1 hybrid, and B10 mice, 2) to compare qualitative and quantitative expression of MBP and MBP-like transcripts in the CNS and thymus of mice suffering from relapsing EAE, 3) to characterize the quantitative and qualitative expression of MBP and MBP-like transcripts in B cells, T cells, macrophages and microglial cells, 4) to determine whether the qualitative and quantitative expression of MBP and MBP-like transcripts in the above cells and tissues is influenced by inflammatory cytokines or other stimulatory molecules, and 5) to determine whether MBP- like transcripts present are translated into protein products in the thymus, CNS and immune cells.
