Organization of the mouse ASGR1 gene encoding the major subunit of the hepatic asialoglycoprotein receptor

The hepatic asialoglycoprotein receptor was the first of the mammalian lectins to be recognized and has been the subject of intense investigation for three decades. Yet, the precise biological role of this major hepatic endocytic receptor has remained elusive. We describe here the characterization of the mouse gene for the major subunit of this receptor (ASGR1) along with 3.5 kb of the upstream 5' region. The gene comprises eight coding exons, with the major transcript in liver displaying a single non-coding 5' exon. A minor hepatic transcript initiates 435 bp upstream of the major start and includes an additional 5' non-coding exon and intron. A minimal 600 bp proximal region of ASGR1 exhibits hepatic-specific promoter activity in HepG2 cells in vitro. These results provide the basis for more detailed genetic studies on the functional role of the hepatic asialoglycoprotein receptor in mammals.