Characterization and functional studies of the mouse biliary glycoprotein (Bgp) genes

Adhesion molecules are present throughout embryonic development and during several physiological and pathological processes. Biliary glycoproteins (Bgp) are cell adhesion molecules that belong to the carcinoembryonic antigen (CEA) family, a member of the Ig supergene family. In an attempt to develop a relevant mouse model, we characterized the gene organization, regulation and expression patterns of the mouse Bgp1 gene. The mouse Bgp1 gene is down-regulated upon tumor transformation. This phenomenon has been correlated with a change in the methylation state of the promoter region of the mouse Bgp1 gene. Two other Cea-related genes, called the Bgp2 and Bgp3 genes, that also belong to the mouse Bgp gene family according to their deduced amino acid sequences and phylogenetic analyses, have also been characterized. Thus, three Bgp genes exist in the mouse genome while a unique BGP gene is found in the human genome. We have demonstrated that the Bgp2 gene product can also act in vitro as an alternative receptor for the mouse hepatitis virus. However, the expression pattern of the mouse Bgp2 gene is less abundant in the colon which is the natural route for MHV infection. Interestingly, the mouse Bgp3 gene presents a gene organization that resembles that of the pregancy specific (Psg) genes, another Cea-related gene subgroup. Expression patterns as well as phylogenetic studies suggest that the Bgp3 gene may represent an evolutionary link between the Cea subgroup and the Psg subgroup. The question remains open regarding the role of Bgp either during embryogenesis and during tumor development. Our studies on the different mouse Bgp gene expression and organization will render a gene ablation approach possible