Genomic organization of the mouse Lmp-2 gene and characteristic structure of its promoter.

Major histocompatibility complex (MHC) class-I molecules present antigenic peptide fragments to cytotoxic T-cells. The peptides are generated in the course of antigen processing from endogenously synthesized cytosolic proteins, and transported into the endoplasmic reticulum to associate with an MHC class-I molecule. So far, at least four genes, Lmp-2, -7, and Tap-1, -2, have been identified between the Pb and Ob genes of the mouse MHC class-II region. The genomic organization of mouse Lmp-2, a gene encoding a subunit of a large intracellular protein complex, was studied. A genomic clone has been isolated that covers the entire mouse Lmp-2 gene. We have determined the nucleotide sequence of the region encompassing the whole Lmp-2 gene and three exons of Tap-1, which spans 8 kb in the mouse genome. The two genes are situated in opposite directions. The transcription start points (tsp) of the two genes, identified by primer extension analysis, are only 118 bp apart. Both promoter regions upstream from the tsp have neither TATA consensus sequences nor other regulatory elements, like an interferon-response element, in spite of their interferon-inducible expression. The Lmp-2 sequence from a non-obese diabetic (NOD) mouse, a model animal for autoimmune diabetes, was compared with that from a Balb/c mouse.