huSCAP Mouse
Product Name
huSCAP Mouse
Product ID
C001950
Strain Name
C57BL/6NCya-Scaptm1(hSCAP)/Cya
Backgroud
C57BL/6NCya
Status
When using this mouse strain in a publication, please cite “huSCAP Mouse (Catalog C001950) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
Gene Alias
--
NCBI ID
Chromosome
Chr 3
MGI ID
Datasheet
Strain Description
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.
Reference
Kober DL, Radhakrishnan A, Goldstein JL, Brown MS, Clark LD, Bai XC, Rosenbaum DM. Scap structures highlight key role for rotation of intertwined luminal loops in cholesterol sensing. Cell. 2021 Jul 8;184(14):3689-3701.e22.
Xu S, Smothers JC, Rye D, Endapally S, Chen H, Li S, Liang G, Kinnebrew M, Rohatgi R, Posner BA, Radhakrishnan A. A cholesterol-binding bacterial toxin provides a strategy for identifying a specific Scap inhibitor that blocks lipid synthesis in animal cells. Proc Natl Acad Sci U S A. 2024 Feb 13;121(7):e2318024121.
Gao Y, Zhou Y, Goldstein JL, Brown MS, Radhakrishnan A. Cholesterol-induced conformational changes in the sterol-sensing domain of the Scap protein suggest feedback mechanism to control cholesterol synthesis. J Biol Chem. 2017 May 26;292(21):8729-8737.
Strain Strategy
The sequences from upstream of exon 1 to 3’UTR of the mouse Scap gene were replaced with the sequences from upstream of exon 1 to 3’UTR of the human SCAP gene.
Figure 1. Diagram of the gene editing strategy for the generation of huSCAP mice.
Application Area
Screening, development, and preclinical evaluation of SCAP-targeted drugs;
Research on the pathological mechanisms and treatment methods of diseases such as metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), autosomal dominant hypercholesterolemia, and hyperlipidemia.
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