huSCAP Mouse
제품명
huSCAP Mouse
제품 ID
C001950
품종 계통
C57BL/6NCya-Scaptm1(hSCAP)/Cya
Backgroud
C57BL/6NCya
상태
이 마우스 계통을 논문에서 사용할 경우, “huSCAP Mouse (카탈로그 번호 C001950)은 Cyagen에서 구입하였습니다.”라고 명시해 주시기 바랍니다.
구매 가능한 제품 종류
연령
Genotype
성별
수량
유전자명
유전자 별칭
--
NCBI ID
염색체
Chr 3
MGI ID
Datasheet
품종 계통 설명
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.
변형 전략
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.
응용 분야
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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