B6-hGLP-1R Mouse
製品名
B6-hGLP-1R Mouse
製品ID
C001421
系統名
C57BL/6NCya-Glp1rtm1(hGLP1R)/Cya
背景情報
C57BL/6NCya
状況
このマウス系統を論文で使用する場合は、「B6-hGLP-1R Mouse（カタログ番号C001421）はサイアジェンから購入しました。」と引用してください。
製品タイプ
年齢
遺伝子型
性別
数量
遺伝子名
遺伝子別名
GLP-1, GLP-1R, GLP-1-R
NCBI ID
染色体
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].
B6-hGLP-1R mice are a model of mouse Glp1r gene humanization, in which the sequences encoding the seven-transmembrane (7TM) structural domain and the larger extracellular structural domain of the human GLP1R gene were inserted into the mouse Glp1r gene sequence using gene editing technology. This model expresses the key functional regions of the human GLP-1R protein while preserving the signal peptide and 3’UTR region of mouse GLp1r. It can be used to study the pathogenesis of various metabolic diseases, such as obesity and type II diabetes, as well as for screening in GLP-1RA drug development. Homozygous B6-hGLP-1R mice are viable and fertile.
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.
Saxena AR, Gorman DN, Esquejo RM, Bergman A, Chidsey K, Buckeridge C, Griffith DA, Kim AM. Danuglipron (PF-06882961) in type 2 diabetes: a randomized, placebo-controlled, multiple ascending-dose phase 1 trial. Nat Med. 2021 Jun;27(6):1079-1087.
Christou GA, Katsiki N, Blundell J, Fruhbeck G, Kiortsis DN. Semaglutide as a promising antiobesity drug. Obes Rev. 2019 Jun;20(6):805-815.
Pratt E, Ma X, Liu R, Robins D, Haupt A, Coskun T, Sloop KW, Benson C. Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1a, blinded, placebo-controlled, randomized, single- and multiple-ascending-dose study in healthy participants. Diabetes Obes Metab. 2023 Sep;25(9):2634-2641.
系統作製戦略
Part of the exon 1 sequence and part of the intron 1 sequence in the mouse Glp1r gene were 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.
Figure 1. Gene editing strategy for B6-hGLP-1R 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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