Tumor necrosis factor stimulated gene-6 (TSG-6) has been previously shown to be induced in vitro in several cell types by proinflammatory cytokines, and in vivo in pathological conditions such as rheumatoid arthritis. In this study, we report the complete coding sequence for the mouse TSG-6 protein, and the exon intron structure and the chromosomal localization of the gene. We have identified a 1605 nt cDNA sequence from mouse cumulus cell oocyte complexes (COCs) induced to expand in vivo. The sequence contains an open reading frame of 825 nt that codes for the 275 amino acid TSG-6 protein. The gene contains six exons separated by 1.1-5.8 kb introns and has been localized to the murine chromosome 2 by linkage analysis. Comparative reverse transcription-polymerase chain reaction studies have revealed that TSG-6 mRNA is specifically expressed after COC expansion induced in vivo, identifying the first non-pathological process in which TSG-6 may play an important role. Since TSG-6 binds to hyaluronan and interacts with inter-alpha-trypsin inhibitor (IalphaI), molecules that are essential for matrix formation by COCs, this protein may have a structural role in the matrix or may enhance the antiproteolytic effect of IalphaI to protect the matrix from degradation.