FVB/N-Tmc1^em1Ftpl/J

Stock number: 036344
Product name: Tmc1 T416K
Research areas: Neurobiology Research, Sensorineural Research

Description

Tmc1 T416K mice carry a CRISPR/Cas9-generated T416K mutation in exon 12 of the mouse Tmc1 (transmembrane channel-like gene family 1) gene that is homologous to a new dominant human deafness mutation, TMC1 p.T422K. Both heterozygous and homozygous mice demonstrate outer hair cell loss and deafness by 4 weeks of age.

Detailed description

Tmc1 (transmembrane channel-like gene family 1) is a major component of the mechanoelectrical transducer (MET) channel in cochlear hair cells and is subject to numerous mutations causing deafness.

Tmc1 T416K mice carry a CRISPR/Cas9-generated T416K mutation in exon 12 of the mouse Tmc1 gene that is homologous to a new dominant human deafness mutation, TMC1 p.T422K. The level of TMC1 expression is unchanged by the mutation, as determined by an antibody test. Both heterozygous and homozygous mice demonstrate outer hair cell loss and deafness by 4 weeks of age. MET channels show decreased Ca²⁺ permeability (due to the introduction of a positively-charged amino acid in the putative pore) and resting open probability, but no change in single-channel conductance or expression.

Development

A T416K (ACC->AAG) mutation was introduced to exon 12 of the mouse Tmc1 gene to modify residues near the putative channel pore via CRISPR/Cas9 methodologies. A silent mutation was also added to create a Dde1 restriction enzyme site. This strain was maintained on an FVB genetic background by the donating laboratory. Mice were bred for 5 generations to help remove any off-target effects.

Allele

Symbol: Tmc1^em1Ftpl
Name: endonuclease-mediated mutation 1, Robert Fettiplace
MGI accession ID: MGI:6715678
Generation method: Endonuclease-mediated
Attributes: Humanized sequence
Synonyms: Tmc1 p.T416K
Marker symbol: Tmc1
Marker name: transmembrane channel-like gene family 1
Marker synonyms: 4933416G09Rik; Beethoven; Bth; DFNA36; DFNB11; DFNB7
Chromosome: 19
Strain of origin: FVB/N
Molecular note: CRISPR/cas9 genome editing is used to introduce a T416K (AAC to AAG) mutation to exon 12 to modify residues near the putative channel pore. A silent mutation was also added to create a Dde1 restriction enzyme site. The mutation is homologous to the pathogenic human T422K mutation.