huTGFBI-R124H Mouse

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.