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.

The Cadherin 16 (CDH16) gene encodes a calcium-dependent, membrane-associated glycoprotein that belongs to the calmodulin superfamily. This cell adhesion molecule is involved in embryonic development and cell growth and is exclusively expressed in the kidney, where it is also known as kidney-specific calmodulin (ksp-calmodulin). CDH16 functions as a major mediator of homotypic cell recognition and plays a role in directing tissue morphogenesis, particularly in the formation of renal tubules during embryonic development. Cdh16-MerCreMer mice were generated by inserting a tamoxifen-inducible Cre recombinase protein (MerCreMer) expression element downstream of the stop codon of the mouse Cdh16 gene. The expression pattern of MerCreMer mirrored that of the endogenous gene. Before induction, MerCreMer was localized to the cytoplasm, and only after tamoxifen treatment could it translocate to the nucleus to exert its recombination effect. When bred with mice containing a loxP site-flanked sequence, Cre recombinase-mediated deletion of the flanked sequence will occur in the renal tubular epithelial cells of the offspring following tamoxifen induction.

Tafa5 is located on chromosome 15 of mice. Nuclease Technology was used to design sgRNA; Tafa5 knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

4930432M17Rik is located on chromosome 3 of mice. Nuclease Technology will be used to design sgRNA; 4930432M17Rik knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

4930432M17Rik is located on chromosome 3 of mice. SgRNA and ssDNA will be designed using Nuclease Technology; 4930432M17Rik conditional knockout mice will be obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm will be collected for cryopreservation.