The mouse cartilage-derived retinoic acid-sensitive protein (Cdrap/Mia) gene is expressed primarily in cartilage. Various promoter motifs that participate in restricted gene expression have been identified. To define mechanisms of regulation further, we determined the DNA sequence of 12 kb flanking this gene. We show that two genes, Snrpa and Rab4b, that have characteristics of housekeeping genes, including ubiquitous expression, closely flank Cdrap/Mia. We found the exon/intron structure and the organization of the gene locus to be conserved between the mouse and the human chromosomes, suggestive of functional relevance. DNase I hypersensitivity assays comparing expressing and nonexpressing cells indicate that the chromatin structure surrounding Cdrap/Mia is not greatly altered for transcription. The tissue-restricted expression of Cdrap/Mia, located between two housekeeping genes, provides a distinctive model for restricted transcriptional regulation from a multigenic locus.