This study focuses on creating a genomically humanized mouse model to investigate DFNA9, a form of adult-onset progressive hearing impairment caused by mutations in the COCH gene. The researchers replaced the murine Coch exons 3-6 with the corresponding human sequences, introducing the c.151C>T mutation associated with DFNA9. To ensure proper splicing and function, human-specific amino acids were converted to their mouse equivalents, and splicing was optimized for the murine system.
The humanized Coch mice exhibited correct splicing of the introduced human exons and maintained normal hearing thresholds at 9 months of age. This indicates that the genomic humanization and splicing optimization were successful. Ongoing studies aim to monitor the mice for late-onset hearing and balance defects, characteristic of DFNA9, to further validate the model.
The mouse model was engineered by replacing the endogenous murine Coch exons 3-6 with human COCH exons containing the c.151C>T mutation. This approach aimed to study the pathogenic mechanisms of DFNA9 and evaluate potential sequence-specific genetic therapies.
Hearing loss, DFNA9, COCH gene, Genomically humanized mouse model, Pre-mRNA splicing
Gene replacement, Humanized mouse model, Exon substitution, Splicing optimization, Hearing assessment
From model design to experimental results
Tailor-made solutions adapted to scientific questions
Comprehensive dataset package
Generated with biopharma partners and in-house
Scientific follow-up and advice along the project
Collaborative approach for problem solving and development of innovative models
Breeding facilities in US and Europe
Certified health status from professional breeders
