The mouse and human IGSF6 (DORA) genes map to the inflammatory bowel disease 1 locus and are embedded in an intron of a gene of unknown function

We have previously characterized IGSF6 (DORA), a novel member of the immuno globulin superfamily (IGSF) from human and rat expressed in dendritic and m yeloid cells. Using a probe from the open reading frame of the rat cDNA, we isolated a cosmid which contains the entire mouse gene. By comparative ana lysis and reverse transcriptase polymerase chain reaction, we defined the i ntron/exon structure and the mRNA of the mouse gene and, with respect to hu man BAC clones, the human gene. The genes span 10 kb (mouse) and 12 kb (hum an), with six exons arranged in a manner similar to other members of the IG SF. All intron/exon boundaries follow the GT-AG rule. Expression of the mou se Igsf6 gene is restricted to cells of the immune system, particularly mac rophages. Northern blot revealed a single mRNA of 2.5 kb, in contrast to th e human gene which is expressed as two mRNAs of 1 and 2.5 kb. The human and mouse genes were localized to a locus associated with inflammatory bowel d isease. Analysis of the flanking regions of the Igsf6 gene revealed the pre sence of an unrelated gene, transcribed from the opposite strand of the DNA and oriented such that the Igsf6 gene is encoded entirely within an intron . An identical organization is seen in human. This gene of unknown function is transcribed and processed, contains homologues in Caenorhabditis elegan s and prokaryotes, and is expressed in most organs in the mouse.