C33 Ag (CD82) is a member of the transmembrane 4 superfamily (TM4SF) and an activation Ag of T-cells. Recent studies have shown that CD82 associates with CD4 or CD8 and delivers costimulatory signals for the TCR/CD3 pathway. We have isolated cDNA and genomic clones of mouse CD82. Mouse CD82 has 266 amino acid residues with 76% identity to human CD82. The mouse CD82 gene consists of nine exons and spans more than 20 kb of genomic DNA. The genomic organization of CD82 is quite similar to that of three other TM4SF members whose genomic structures were described, i.e., Tapa-1 (CD81), CD53, and CD63. By mapping the 5' end of CD82 transcripts, we found a single major transcription initiation site 144 bp upstream of the ATG initiation codon. We also determined the sequence of the 5' flanking region of CD82 gene for about 2 kb. The 5' nanking sequence has a housekeeping promoter with potential binding motifs for various transcriptional factors. Northern blot analysis showed quite variable expression of the CD82 gene among different organs. The highest expression was seen in the spleen and the kidney. The expression was low in skeletal muscle and hardly detectable in the heart. Northern blot analysis was also carried out for CD81, CD53, and CD63. The expression of the CD81 gene was ubiquitous and similar among different organs, while that of CD53 was seen only in the spleen. The expression of the CD63 gene was ubiquitous, with the highest expression in the kidney. These results together with the comparison of the structures of 5' flanking sequences of these genes indicate distinct regulations of gene expression for these four members of TM4SF. (C) 1994 Academic Press, Inc.
