Asialoglycoprotein receptor deficiency in mice lacking the major receptor subunit - Its obligate requirement for the stable expression of oligomeric receptor

The asialoglycoprotein receptor is an abundant hetero-oligomeric endocytic receptor that is predominantly expressed on the sinusoidal surface of the h epatocytes, A number of physiological and pathophysiological functions have been ascribed to this hepatic lectin (HL), the removal of desialylated ser um glycoproteins and apoptotic cells, clearance of lipoproteins, and the si tes of entry for hepatotropic viruses. The assembly of two homologous subun its, HL-1 and HL-2, is required to form functional, high affinity receptors on the cell surface. However, the importance of the individual subunits fo r receptor transport to the cell surface is controversial. We have previous ly generated HL-S-deficient mice and showed that the expression of HL-1 was significantly reduced, and the functional activity as the asialoglycoprote in receptor was virtually eliminated. However, we failed to detect phenotyp ic abnormalities. To explore the significance of the major HL-1 subunit for receptor expression and function in vivo, we have disrupted the HL-1 gene in mice. Homozygous HL-1-deficient animals are superficially normal. HL-2 e xpression in the liver is virtually abrogated, indicating that HL-1 is stri ctly required for the stable expression of HL-2, Although these mice are al most unable to clear asialo-orosomucoid, a high affinity ligand for asialog lycoprotein receptor, they do not accumulate desialylated glycoproteins or lipoproteins in the plasma.