B6-hFBN1 Mouse

Marfan syndrome (MFS) is an autosomal dominant systemic connective tissue disorder with a prevalence of 1/3,000–1/5,000, unaffected by race or geographic location. Patients typically exhibit disproportionately long limbs, fingers, and toes, and significantly exceed average height. Clinically, the disease presents with diverse manifestations, with the most life-threatening complications involving the cardiovascular system, including mitral valve prolapse, aortic valve regurgitation, aortic root dilation, and aortic dissection. This connective tissue disorder affects multiple organ systems, including the skeletal, pulmonary, ocular, central nervous, and cardiovascular systems ^[1]. The FBN1 gene is the causative gene for MFS, which encodes fibrillin-1, a connective tissue protein that provides structural support to cells as an extracellular matrix component and imparts elasticity and strength to connective tissues. FBN1 mutations can lead to a spectrum of type I fibrillinopathies, including Marfan syndrome (MFS), dominant Weill-Marchesani syndrome, and scleroderma.

Current therapeutic strategies for MFS primarily focus on preventive and symptomatic treatments, while gene therapy, potentially addressing both prevention and symptom management, shows promise as the next frontier in research. Studies have demonstrated that gene editing technologies can correct mutations in patient-derived induced pluripotent stem cells (iPSCs), marking a critical first step toward developing efficient and precise gene therapies for MFS ^[2-3]. Subsequent in vivo animal studies are indispensable for preclinical research. As gene therapies act on the human FBN1 gene, the development of fully humanized animal models is scientifically robust and adaptable to diverse drug targeting sites, accelerating the FBN1-targeted therapeutic approaches into clinical trials.

The B6-hFBN1 mouse is a humanized model, generated by in situ replacement of the mouse Fbn1 gene sequence (including 3'UTR) with the corresponding human FBN1 sequence while retaining the mouse signal peptide. This model is suitable for research on the pathogenesis and therapeutic agents for Marfan syndrome (MFS), dominant Weill-Marchesani syndrome, scleroderma, and other related disorders. Additionally, leveraging its proprietary TurboKnockout fusion BAC recombination technology, Cyagen can provide popular mutation disease models based on this platform or offer customized services for different mutations to meet the experimental needs of researchers.