B6-hGLP-1R/ob Mouse
製品名
B6-hGLP-1R/ob Mouse
製品ID
C001601
系統名
C57BL/6NCya;C57BL/6JCya-Glp1rtm1(hGLP1R)Lepem1(R105X)/Cya
背景情報
C57BL/6NCya;C57BL/6JCya
状況
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製品タイプ
年齢
遺伝子型
性別
数量
遺伝子別名
ob, obese, GLP-1, GLP-1R, GLP-1-R
染色体
Chr 6, Chr 6
MGI ID
さらに
系統詳細
The Glucagon-like peptide 1 receptor (GLP1R) gene encodes a protein that belongs to the glucagon receptor subfamily of the G protein-coupled receptor B cluster [1]. This cell surface receptor protein is widely expressed in tissues such as the brain, small intestine, heart, and lungs, and plays a crucial role in insulin secretion signaling cascades by responding to GLP-1 and GLP-1 analogs. Animal model data also suggest that it has neuroprotective effects. Polymorphisms of this gene are closely associated with diabetes, making the GLP-1R protein an important drug target for the treatment of type 2 diabetes and stroke [2-3]. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are novel anti-diabetic drugs that activate GLP-1R to enhance insulin secretion, inhibit glucagon secretion, delay gastric emptying, and reduce food intake through central appetite suppression, thereby achieving blood sugar reduction and weight loss [4].
The leptin (LEP) gene, also known as the OB gene, encodes the leptin protein, which is secreted into the circulation by white adipocytes and plays a major role in regulating energy homeostasis. Circulating leptin binds to leptin receptors (LEPR) in the brain, activating downstream signaling pathways that inhibit feeding and promote energy expenditure. Leptin also has multiple endocrine functions and is involved in physiopathological processes such as immune and inflammatory responses, hematopoiesis, angiogenesis, reproduction, bone formation, and wound healing [6]. Mutations in the LEP gene and its regulatory regions lead to severe obesity and morbid obesity with hypogonadism in humans and are also associated with the development of type II diabetes [7].
The B6-hGLP-1R/ob mouse model, generated by mating B6-hGLP-1R mice (Catalog Number: C001421) with Lep KO (ob/ob) mice (Catalog Number: C001368), is a metabolic disease model. It can be used for research on the pathogenic mechanisms of various metabolic diseases, such as obesity and type II diabetes, and for screening GLP-1RA drugs.
参考文献
Blad CC, Tang C, Offermanns S. G protein-coupled receptors for energy metabolites as new therapeutic targets. Nat Rev Drug Discov. 2012 Aug;11(8):603-19.
Yun SP, Kam TI, Panicker N, Kim S, Oh Y, Park JS, Kwon SH, Park YJ, Karuppagounder SS, Park H, Kim S, Oh N, Kim NA, Lee S, Brahmachari S, Mao X, Lee JH, Kumar M, An D, Kang SU, Lee Y, Lee KC, Na DH, Kim D, Lee SH, Roschke VV, Liddelow SA, Mari Z, Barres BA, Dawson VL, Lee S, Dawson TM, Ko HS. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease. Nat Med. 2018 Jul;24(7):931-938.
Schonhoff AM, Harms AS. Glial GLP1R: A novel neuroprotector? Mov Disord. 2018 Dec;33(12):1877.
Andreasen CR, Andersen A, Knop FK, Vilsbøll T. Understanding the place for GLP-1RA therapy: Translating guidelines for treatment of type 2 diabetes into everyday clinical practice and patient selection. Diabetes Obes Metab. 2021 Sep;23 Suppl 3:40-52.
Laviola L, Leonardini A, Melchiorre M, Orlando MR, Peschechera A, Bortone A, Paparella D, Natalicchio A, Perrini S, Giorgino F. Glucagon-like peptide-1 counteracts oxidative stress-dependent apoptosis of human cardiac progenitor cells by inhibiting the activation of the c-Jun N-terminal protein kinase signaling pathway. Endocrinology. 2012 Dec;153(12):5770-81.
Ahima RS, Flier JS. Leptin. Annu Rev Physiol. 2000;62:413-37.
Livshits G, Pantsulaia I, Gerber LM. Association of leptin levels with obesity and blood pressure: possible common genetic variation. Int J Obes (Lond). 2005 Jan;29(1):85-92. doi: 10.1038/sj.ijo.0802826. Erratum in: Int J Obes Relat Metab Disord. 2005 Apr;29(4):447.
系統作製戦略
Construction strategy for B6-hGLP-1R mice: Part of the exon 1 sequence and part of the intron 1 sequence in the mouse Glp1r gene was replaced with “hGLP1R Exon 1~2 CDS (without signal peptide), hGLP1R Intron 2 and hGLP1R Exon 3~13 CDS - mGlp1r 3’UTR - hGH pA” while retaining the gene sequence encoding the signal peptide of the mouse Glp1r protein.
Construction strategy for Lep KO (ob/ob) mice: A p.R105*(CGA to TGA) mutation was introduced into exon 3 of the Lep gene in C57BL/6JCya mice.
Figure 1. Diagram of the gene editing strategy for the generation of B6-hGLP-1R mice.
Figure 2. Diagram of the gene editing strategy for the generation of Lep KO(ob/ob) mice.
適用分野
Investigation of the pathogenesis of obesity and type 2 diabetes；
Development and screening of drugs for obesity and type 2 diabetes；
Research on other metabolic diseases such as cardiovascular and myocardial diseases <sup>[5]</sup>；
Study of the neuroprotective effect in nervous system diseases.
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