C57BL/6NCya-Asgr1^em1flox/Cya

Asgr1, also known as asialoglycoprotein receptor 1, is a C-type lectin receptor [4]. It is primarily expressed in the liver and mediates the internalization and lysosomal degradation of blood asialoglycoproteins. Asgr1 is involved in cholesterol metabolism and also plays a role in the body's response to liver injury and sepsis-induced liver injury [1,2,3]. Genetic models, such as gene knockout mouse models, have been crucial for studying its functions.

In gene knockout mouse models, Asgr1 deficiency has been shown to have multiple effects. It decreases lipid levels in serum and liver by stabilizing LXRα, which upregulates ABCA1 and ABCG5/G8, promoting cholesterol transport to high-density lipoprotein and excretion to bile and faeces, respectively [1]. Additionally, Asgr1 deficiency exacerbates liver injury in male mice, as it increases circulating levels of GP73, a mediator of endoplasmic reticulum stress, leading to liver injury [2]. In sepsis-induced liver injury, ASGR1-knockdown mice show suppressed monocyte-to-macrophage differentiation, alleviated liver injury, and improved survival [3]. In ApoE-/-mice, Asgr1 deficiency improves atherosclerosis but also causes broader alterations in liver metabolism and a deterioration of liver injury [5].

In conclusion, Asgr1 plays essential roles in cholesterol metabolism, liver injury, and sepsis-induced liver injury as revealed through gene knockout mouse models. These studies contribute to understanding the biological functions of Asgr1 in related disease areas, such as hypercholesterolemia, liver diseases, and sepsis-related liver injuries, providing potential directions for therapeutic interventions [1,2,3,5].