B6-hCFTR*F508del Mouse
製品名
B6-hCFTR*F508del Mouse
製品ID
I001226
系統名
C57BL/6NCya-Cftrtm2(hCFTR c.1521_1523 del CTT)/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-hCFTR*F508del Mouse（カタログ番号I001226）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
CF, MRP7, ABC35, ABCC7, CFTR/MRP, TNR-CFTR, dJ760C5.1
NCBI ID
染色体
Chr 7
MGI ID
さらに
系統詳細
The cystic fibrosis transmembrane conductance regulator (CFTR) is a critical protein that maintains the salt and water balance across various human organs, including the lungs, pancreas, and sweat glands. The primary function of CFTR is to act as a chloride channel, regulating the transport of chloride and bicarbonate ions across epithelial cell membranes, thereby maintaining tissue fluid balance and pH. This process is ATP-dependent and also modulates the activity of other ion channels and transport proteins [1-2]. Mutations in the CFTR gene can lead to chloride channel dysfunction, resulting in various diseases, with cystic fibrosis (CF) being the most common. CF is the most prevalent lethal genetic disease among Caucasians, with an incidence of approximately 1/2,500 to 1/1,800, and about 90,000 cases globally [3-4]. The disease is characterized by thickened mucus in the lungs, frequent respiratory infections, pancreatic insufficiency, and male infertility, typically due to vas deferens obstruction. The F508del (ΔF508) mutation is the most common pathogenic mutation in CF, with about 80% of CF patients carrying at least one allele of this mutation, and approximately 40% being homozygous [5]. This mutation causes the deletion of phenylalanine (F508) in the first nucleotide-binding domain (NBD1) of the CFTR protein, leading to misfolding and endoplasmic reticulum (ER)-mediated degradation, preventing CFTR from reaching the cell membrane and compromising chloride channel function, which results in chronic pulmonary symptoms [6-7]. Current treatments for CF mainly focus on CFTR modulators to restore the function of the mutated CFTR protein. CFTR modulators are classified into potentiators (which enhance CFTR function) and correctors (which assist in the proper folding and trafficking of CFTR to the cell membrane). Representative drugs include Ivacaftor, Lumacaftor, and triple-combination CFTR modulating therapy Elexacaftor-Tezacaftor-Ivacaftor [8].
This strain was developed by introducing the F508del mutation into the CFTR-humanized mouse model (Catalog Number: C001964), creating a humanized disease model. The introduction of the mutation results in the manifestation of CF-related phenotypes in mice, making it suitable for research into CF mechanisms and the screening, development, and evaluation of therapies targeting the CFTR F508del mutation. This strain requires feeding with intestinal cleansers to maintain survival after 3 weeks of age. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen can also generate hot mutation models based on the CFTR-humanized strain and provide customized services for specific mutations to meet the experimental needs in pharmacology and other fields.
参考文献
Corradi V, Vergani P, Tieleman DP. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR): CLOSED AND OPEN STATE CHANNEL MODELS. J Biol Chem. 2015 Sep 18;290(38):22891-906.
Csanády L, Vergani P, Gadsby DC. STRUCTURE, GATING, AND REGULATION OF THE CFTR ANION CHANNEL. Physiol Rev. 2019 Jan 1;99(1):707-738.
Chillón M, Casals T, Mercier B, Bassas L, Lissens W, Silber S, Romey MC, Ruiz-Romero J, Verlingue C, Claustres M, et al. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med. 1995 Jun 1;332(22):1475-80.
Grasemann H, Ratjen F. Cystic Fibrosis. N Engl J Med. 2023 Nov 2;389(18):1693-1707.
Lopes-Pacheco M. CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine. Front Pharmacol. 2020 Feb 21;10:1662.
Hoelen H, Kleizen B, Schmidt A, Richardson J, Charitou P, Thomas PJ, Braakman I. The primary folding defect and rescue of ΔF508 CFTR emerge during translation of the mutant domain. PLoS One. 2010 Nov 30;5(11):e15458.
He L, Skirkanich J, Moronetti L, Lewis R, Lamitina T. The cystic-fibrosis-associated ΔF508 mutation confers post-transcriptional destabilization on the C. elegans ABC transporter PGP-3. Dis Model Mech. 2012 Nov;5(6):930-9.
Valladares KN, Jones LI, Barnes JW, Krick S. Highly Effective Modulator Therapy: Implications for the Microbial Landscape in Cystic Fibrosis. Int J Mol Sci. 2024 Nov 5;25(22):11865.
系統作製戦略
Figure 1. Construction strategy for the B6-hCFTR wild-type humanized model (Catalog Number: C001964): The region from 5'UTR to 3'UTR of mouse Cftr gene was replaced with the region from 5'UTR to 3'UTR of human CFTR gene.
Figure 2. Construction strategy for the B6-hCFTR*F508del point mutation humanized model (Catalog Number I001226): Gene editing technology was used to introduce the F508del mutation (c.1521_1523 delCTT) into exon 11 of the human CFTR gene in the B6-hCFTR mouse.
適用分野
This strain is suitable for studying the mechanisms underlying cystic fibrosis and evaluating targeted therapies in terms of their efficacy and pharmacodynamics.
お問い合わせ
カスタムの動物モデルに関するご相談は、下記のフォームにご記入いただき、ご連絡いただくか見積もりをご依頼ください。
Cyagenはお客様のプライバシーを大変重視しています。当社の最新の製品や情報をお届けしたいと思っています。お客様の設定をご確認ください。
これらの配信はいつでも解除できます。配信停止方法およびデータ保護の詳細は プライバシーポリシー をご確認ください。
以下のボタンをクリックすることで、このフォームにご入力いただいた個人情報をCyagenが保存・処理し、ご要望のコンテンツを提供することに同意されたことになります。