The SCAP gene (SREBP cleavage-activating protein) encodes a critical regulatory protein that functions as a sterol sensor and escort within the cell. Primarily expressed in the liver, brain, and endocrine tissues, the SCAP protein resides in the endoplasmic reticulum (ER) membrane, where it forms a complex with SREBP (Sterol Regulatory Element-Binding Protein) ^[1]. When cellular cholesterol levels are low, SCAP undergoes a conformational change that allows it to escort SREBPs to the Golgi apparatus for activation, thereby triggering the expression of genes involved in lipid synthesis ^[2]. Conversely, high sterol levels cause SCAP to bind to INSIG proteins, anchoring the complex in the ER and halting lipid production ^[3]. Due to its central role in metabolic homeostasis, dysregulation of the SCAP gene is associated with metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and hyperlipidemia, while specific mutations have been linked to autosomal dominant hypercholesterolemia. huSCAP mice are humanized models generated using gene editing technology by replacing the sequences from upstream of exon 1 to 3’UTR of the mouse Scap gene with the sequences from upstream of exon 1 to 3’UTR of the human SCAP gene. This strain can be used for studying the pathological mechanisms and treatments of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), autosomal dominant hypercholesterolemia, and hyperlipidemia, as well as for the development of SCAP-targeted drugs.

AU021092 is located on chromosome 16 of mice. Nuclease Technology will be used to design sgRNA; AU021092 knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.