STOCK Tmc1^em2Ftpl/J

Stock number: 036345
Product name: Tmc1 W554L
Research areas: Neurobiology Research, Sensorineural Research

Description

Tmc1 W554L mice carry a recessive CRISPR/Cas9-generated W554L mutation in exon 15 of the mouse Tmc1 (transmembrane channel-like gene family 1) gene. Homozygotes develop progressive hearing loss by 8 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 W554L mice carry a recessive CRISPR/Cas9-generated W554L mutation in exon 15 of the mouse Tmc1 gene. A decrease in TMC1 expression has been observed in cochlear hair bundles, as determined by an antibody staining. Heterozygous mice have normal hearing, but homozygotes develop progressive hearing loss by 8 weeks of age.

When combined with a Tmc2 knockout (Tmc2^tm1Lex, MMRRC Stock No. 032627-UCD), mice also have vestibular defects that result in balance problems and circling behavior.

Development

A W554L (TGG->CTG) mutation was introduced to exon 15 of the mouse Tmc1 gene to modify residues near the putative pore of the channel via CRISPR/Cas9 methodologies. Three additional silent mutations were also created to add a BstAP1 enzyme restriction site. The mutations were created in C57BL/6J embryos. Resultant mice were bred to a 129/Sv strain for more than 5 generations to help increase litter sizes by the donating laboratory. Maintenance at The Jackson Laboratory will likely involve 129S1/SvImJ (Stock No. 002448).

A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, was performed on the imported mice. Sixteen of the markers were homozygous for the C57BL/6J allele, and another two markers were heterozygous for the C57BL/6J and 129 alleles. An allele of unknown genetic origin was found on Chromosome 13. (December, 2021)

Allele

Symbol: Tmc1^em2Ftpl
Name: endonuclease-mediated mutation 2, Robert Fettiplace
MGI accession ID: MGI:6715680
Generation method: Endonuclease-mediated
Attributes: Not Applicable
Synonyms: Tmc1 p.W554L
Marker symbol: Tmc1
Marker name: transmembrane channel-like gene family 1
Marker synonyms: 4933416G09Rik; Beethoven; Bth; DFNA36; DFNB11; DFNB7
Chromosome: 19
Strain of origin: C57BL/6J
Molecular note: CRISPR/cas9 genome editing is used to introduce a W554L (TGG to CTG) mutation into exon 15 to modify residues near the putative pore of the channel. Three additional silent mutations were also created to add a BstAP1 enzyme restriction site.