B6.129-Tmc1^tm1.1Ajg/J

Stock number: 019146
Research areas: Mouse/Human Gene Homologs, Neurobiology Research, Research Tools, Sensorineural Research

Description

In this strain an IRES-lacZ cassette replaces exons 8 and 9 of the Tmc1 (transmembrane channel-like gene family 1) gene. These mice develop profound hearing loss.

Detailed description

Mutations of the human TMC1 gene, transmembrane channel-like protein 1, cause certain types of autosomal dominant deafness (DFNA36) and of recessive deafness (DFNB7/B11). These mice carry a targeted mutation in which IRES-lacZ replaces exon 8 and 9 (encoding the first transmembrane domain). Mice that are homozygous for the targeted mutation are viable and fertile, but congenitally deaf. Beta-galactosidase activity is detected in the hair cells of the saccular and utricular maculae, cristae ampullaris and the organ of Corti in the inner ear of heterozygous and homozygous animals as early as P5.

Double mutant mice that are homozygous for the Tmc1^tm1.1Ajg (Stock No. 019146) and Tmc2^tm1.1Ajg (Stock No. 019147) targeted mutation alleles are deaf, exhibit altered vestibulo-ocular reflex and lack mechanotransduction currents in the hair cells.

Development

A targeting vector containing IRES-lacZ sequence and a floxed PGK-NEO cassette was used to disrupt exons 8 and 9. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6-Tg(Zp3-cre)93Knw/J (Stock No. 003651) mice to remove the PKG-NEO cassette. The mice were then backcrossed to C57BL/6J for at least 15 generations.

Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Tmc1^tm1.1Ajg
Name: targeted mutation 1.1, Andrew J Griffith
MGI accession ID: MGI:5427097
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Synonyms: Tmc1^delta
Marker symbol: Tmc1
Marker name: transmembrane channel-like gene family 1
Marker synonyms: 4933416G09Rik; Beethoven; Bth; DFNA36; DFNB11; DFNB7
Chromosome: 19
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: Tmc1 is normally expressed in mouse vestibular and cochlear hair cells and GFP-tagged TMC proteins localizes near stereocilia tips. Beta-galactosidase activity in Tmc1^tm1.1Ajg mutants is detected in the hair cells of the saccular and utricular maculae, cristae ampullaris and the organ of Corti in the inner ear of heterozygous and homozygous animals as early as P5.
Molecular note: Exons 8 and 9 were replaced with an IRES-lacZ cassette and a floxed pgk-neo cassette via homologous recombination. Cre mediated recombination removed the neo cassette. At P28 beta-galactosidase activity is detected in both type I and type II hair cells of the saccular macula, utricular macula, and cristae ampullaris.