B6-huASGR1 Mouse

Asialoglycoprotein receptor 1 (ASGR1), encoded by the ASGR1 gene, is central to cholesterol homeostasis and liver pathophysiology. Primarily localized to the hepatocyte plasma membrane, ASGR1 mediates ligand internalization and lysosomal degradation ^[1-2]. Ligand binding triggers ASGR1-dependent metabolism, involving the formation of a heteromeric complex with ASGR2, which recognizes glycoproteins with terminal galactose or N-acetylgalactosamine residues. Through modulation of the liver X receptor (LXR)/breast cancer susceptibility gene 1 (BRCA1)/BRCA1-associated ring domain protein 1 (BARD1) pathway, ASGR1 facilitates cholesterol excretion into bile, thereby influencing systemic lipid levels ^[1-2]. Beyond cholesterol regulation, ASGR1 participates in liver lesion processes, underscoring its broader role in liver health ^[3]. Notably, loss-of-function mutations in ASGR1 correlate with reduced circulating cholesterol and decreased cardiovascular disease risk. Conversely, elevated serum soluble ASGR1 (sASGR1) levels are associated with increased low-density lipoprotein cholesterol (LDL-C), particularly in hypertensive individuals ^[3]. Consequently, ASGR1 has emerged as a therapeutic target for cardiovascular and hepatic disorders, including hypercholesterolemia, atherosclerosis, non-alcoholic fatty liver disease, and cirrhosis ^[2-4].

The B6-huASGR1 mouse model was generated by replacing sequences from the ATG start codon to the TAG stop codon of the endogenous mouse Asgr1 gene with the sequences from the ATG start codon to the TAA stop codon of the human ASGR1 gene. This model can be used to study the pathological mechanisms and therapeutic approaches for cardiovascular and liver diseases, as well as for the development of ASGR1-targeted drugs.