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Published on: November 13, 2021
Ush1c216A knock-in mouse survives Katrina
Jennifer Lentz1, Fuming Pan, San San Ng
1Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Mutation Research
|December 19, 2006
Summary
Usher syndrome, a genetic disorder causing deafness and blindness, is linked to a specific mutation in the USH1C gene. A new mouse model replicates this mutation, revealing its impact on hearing and balance.
Area of Science:
- Genetics
- Neuroscience
- Ophthalmology
Background:
- Usher syndrome is the leading cause of inherited combined deafness and blindness.
- It involves progressive retinitis pigmentosa, with varying hearing and vestibular impairment.
- Acadian Usher type IC patients harbor a specific splice site mutation in the USH1C gene.
Purpose of the Study:
- To investigate the functional impact of the 216G-->A splice site mutation in the USH1C gene.
- To create and characterize a knock-in mouse model of the human 216G-->A mutation.
Main Methods:
- Developed a targeting construct with homology arms for USH1C gene.
- Used embryonic stem cells for homologous recombination and generated chimeric mice.
- Utilized Cre-lox system for neomycin gene deletion and germline transmission of the mutation.
- Analyzed mouse phenotypes (behavior, Preyer reflex) and performed RT-PCR on cochlea and retina.
Main Results:
- Homozygous Ush1c216A mice exhibited hyperactivity, circling, and head tossing.
- These mice lacked a Preyer reflex, indicating hearing impairment.
- RT-PCR confirmed a 35-base deletion in the cochlea and retina of mutant mice, mirroring Usher IC patients.
- The mutation causes a frame-shift in the harmonin-encoding USH1C gene.
Conclusions:
- The knock-in mouse model successfully replicates the USH1C splice site mutation found in Usher IC patients.
- This model demonstrates the mutation's role in causing hearing and balance deficits.
- It provides a valuable tool for studying Usher syndrome pathogenesis and developing therapies.
