Structural organization and mammary-specific expression of the butyrophilin gene.

Butyrophilin is a glycoprotein of the immunoglobulin superfamily that is secreted in association with the milk-fat-globule membrane from mammary epithelial cells. As a first step towards determining the possible function(s) of this protein in lactation, the mouse butyrophilin gene (Btn) has been cloned from a 129-ES cell genomic library. Over 14 kb of DNA was sequenced, including the entire transcriptional unit of the gene, and 4.6 kb and 1.1 kb of the 5' and 3' flanking region, respectively. In addition, the overall structure of the bovine gene (BTN) was determined by amplification of genomic DNA by the polymerase chain reaction. Both Btn and BTN comprise seven exons and six introns. The signal sequence and two immunoglobulin-like folds of the exoplasmic domain and the membrane anchor are encoded by separate exons, and the cytoplasmic domain is encoded by two short exons and a large terminal exon that also includes 3' untranslated sequence. The butyrophilin gene appears to have evolved from a subset of genes in the immunoglobulin superfamily and genes encoding the B30.2 domain, which is conserved in a family of zinc-finger proteins. Murine butyrophilin mRNA was detected specifically in the mammary gland by RNase protection analysis. Expression increased during the last half of pregnancy and was maximal during lactation. The 5' flanking region of Btn was analyzed for putative regulatory elements and is different from the promoters of other mammary-specific genes. Btn should be useful for determining the mechanisms underlying mammary-specific gene expression and potentially for the production of heterologous proteins in the milk of transgenic animals.