huTGFBI-R124H Mouse
製品名
huTGFBI-R124H Mouse
製品ID
C002005
系統名
C57BL/6JCya-Tgfbitm2(hTGFBI*R124H)/Cya
背景情報
C57BL/6JCya
状況
このマウス系統を論文で使用する場合は、「huTGFBI-R124H Mouse（カタログ番号C002005）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
CSD, CDB1, CDG2, CSD1, CSD2, CSD3, EBMD, LCD1, BIGH3, CDGG1
NCBI ID
染色体
Chr 5
MGI ID
さらに
系統詳細
Corneal dystrophy (CD) refers to a group of primary hereditary progressive corneal diseases. The typical clinical presentation involves gradual loss of corneal transparency in both eyes, often leading to recurrent corneal erosions and visual impairment. The TGFBI gene (also known as BIGH3) encodes an extracellular matrix protein called keratoepithelin (KE protein), which plays a role in cell growth, differentiation, wound healing, cell adhesion, migration, apoptosis, proliferation, and tumorigenesis [1]. Mutations in the TGFBI gene are associated with various types of corneal dystrophy. Abnormal accumulation of mutated TGFBI deposits in the corneal epithelium and stroma progressively affects corneal transparency, leading to visual impairment.
The R124H mutation represents one of the most clinically significant genetic alterations within the TGFBI gene, specifically resulting from a missense mutation. This particular mutation is the definitive genetic cause of Granular Corneal Dystrophy type 2 (GCD2), also historically referred to as Avellino corneal dystrophy [2]. Unlike other variants that may produce a single type of protein deposit, the R124H mutation is characterized by a "mixed" pathology, leading to the simultaneous accumulation of both crumb-like granular deposits and proteinaceous lattice-like amyloid fibrils within the corneal stroma. Furthermore, the R124H mutation is notoriously sensitive to external trauma, meaning that refractive surgeries like LASIK or PRK can trigger a massive, accelerated inflammatory response and a surge in protein deposition, which often necessitates corneal transplantation to restore sight [3]. Thus, developing gene therapy is crucial for this patient population.
huTGFBI-R124H mice are generated by introducing the R124H mutation into the human TGFBI gene and subsequently knocking out exon 13 in huTGFBI mice (Catalog Number: C001546) using gene editing technology. This strain can be used for studying the pathological mechanisms and treatments of Granular Corneal Dystrophy type 2 (GCD2), as well as for the development of TGFBI-targeted drugs.
参考文献
Wang L, Zhao C, Zheng T, Zhang Y, Liu H, Wang X, Tang X, Zhao B, Liu P. Torin 1 alleviates impairment of TFEB-mediated lysosomal biogenesis and autophagy in TGFBI (p.G623_H626del)-linked Thiel-Behnke corneal dystrophy. Autophagy. 2022 Apr;18(4):765-782.
Yamazoe K, Yoshida S, Yasuda M, Hatou S, Inagaki E, Ogawa Y, Tsubota K, Shimmura S. Development of a Transgenic Mouse with R124H Human TGFBI Mutation Associated with Granular Corneal Dystrophy Type 2. PLoS One. 2015 Jul 21;10(7):e0133397.
Park JE, Yun SA, Roh EY, Yoon JH, Shin S, Ki CS. Prevalence of granular corneal dystrophy type 2-related TGFBI p.R124H variant in a South Korean population. Mol Vis. 2021 May 8;27:283-287.
系統作製戦略
Figure 1. Gene editing strategy of huTGFBI (Catalog Number: C001546) mice. The sequences from Eoxn 1 to TAG stop codon of mouse Tgfbi were replaced with the sequences from Eoxn 1 to TAG stop codon of human TGFBI. The murine signal peptide was kept.
Figure 2. Diagram of the gene editing strategy for the generation of huTGFBI-R124H mice. The R124H mutation was introduced into exon 4 of the humanized TGFBI gene in huTGFBI mice. Exon 13 was selected as the KO region.
適用分野
Research on the pathological mechanisms and treatments of Granular Corneal Dystrophy type 2 (GCD2);
Development, screening, and preclinical evaluation of TGFBI-targeted drugs.
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。