Asialoglycoprotein receptor deficiency in mice lacking the minor receptor subunit

The asialoglycoprotein receptor is an abundant heterooligomeric endocytic receptor that is predominantly expressed on the sinusoidal surface of the hepatocytes. Proposed physiological and pathophysiological functions ascribed to this hepatic lectin (HL) include the removal of desialylated serum glycoproteins and apoptotic cells, clearance of chylomicron remnants, and a role as a homing receptor for lymphatic and metastatic cells. The assembly of two homologous subunits, HL-1 and HL-2, is required to form functional, high affinity receptors on the cell surface. However, the importance of the individual subunits for receptor transport to the cell surface has been controversial. To explore the significance of the minor HL-2 subunit for receptor expression and function in vivo, we have disrupted the HL-2 gene in mice. Homozygous HL-2-deficient animals are superficially normal. However, HL-1 expression in the liver is greatly reduced, indicating that HL-2 may promote HL-1 stability. Although these mice are completely unable to clear asialoorosomucoid, a high affinity ligand for asialoglycoprotein receptor, they do not accumulate desialylated glycoproteins or lipoproteins in their circulation.