huCFTR-W1282* Mouse

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 W1282X mutation is a prevalent and severe class I nonsense mutation (c.3846G>A, p.Trp1282Ter) in the CFTR gene, notably common in the Ashkenazi Jewish population ^[5]. This genetic alteration introduces a premature termination codon at position 1282, which prematurely truncates the synthesis of the CFTR protein. Consequently, the resulting shortened polypeptide is unstable and the corresponding mRNA is often degraded via the nonsense-mediated mRNA decay (NMD) pathway, leading to a near-complete absence of functional CFTR protein and an associated severe clinical phenotype of Cystic Fibrosis (CF). 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 ^[6].

huCFTR-W1282* mice were developed by introducing the W1282X mutation into the CFTR-humanized mouse model (Catalog Number: C001964), creating a humanized disease model. It is suitable for research into CF mechanisms and the development of therapies targeting the CFTR W1282X mutation. This strain requires feeding with intestinal cleansers to maintain survival. 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.