Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Heterozygote x Heterozygote         (Female x Male)   19-APR-13 Species laboratory mouse   Donating Investigator Dr. Andrew J. Griffith,   NIDCD/NIH

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.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Tmc1

006169

CBA.Cg-Tmc1dn/AjgJ

View Strains carrying other alleles of Tmc1     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Deafness, Autosomal Dominant 36; DFNA36   (TMC1) Deafness, Autosomal Recessive 7; DFNB7   (TMC1)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Tmc1^tm1.1Ajg/Tmc1^tm1.1Ajg

        B6.129-Tmc1^tm1.1Ajg

• hearing/vestibular/ear phenotype
• abnormal hair cell mechanoelectric transduction
  • significant reduction in current amplitude in outer hair cells from the apical cochlea at P5-P7 but not in cells from the basal turns at P2-P4   (MGI Ref ID J:184419)
• cochlear hair cell degeneration   (MGI Ref ID J:184419)
• • cochlear inner hair cell degeneration
    • starting after P14   (MGI Ref ID J:184419)
  • cochlear outer hair cell degeneration
    • starting after P14   (MGI Ref ID J:184419)
• deafness
  • profound   (MGI Ref ID J:184419)
• increased or absent threshold for auditory brainstem response
  • increased ABR threshold at all frequencies tested   (MGI Ref ID J:184419)
• behavior/neurological phenotype
• *normal* behavior/neurological phenotype
  • normal motor behavior   (MGI Ref ID J:184419)
• nervous system phenotype
• abnormal hair cell mechanoelectric transduction
  • significant reduction in current amplitude in outer hair cells from the apical cochlea at P5-P7 but not in cells from the basal turns at P2-P4   (MGI Ref ID J:184419)
• cochlear hair cell degeneration   (MGI Ref ID J:184419)
• • cochlear inner hair cell degeneration
    • starting after P14   (MGI Ref ID J:184419)
  • cochlear outer hair cell degeneration
    • starting after P14   (MGI Ref ID J:184419)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Mouse/Human Gene Homologs
deafness

Neurobiology Research
Hearing Defects

Research Tools
lacZ Expression
Genetics Research
      Tissue/Cell Markers
Sensorineural Research

Sensorineural Research
Hearing Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tmc1tm1.1Ajg
Allele Name		targeted mutation 1.1, Andrew J Griffith
Allele Type		Targeted (Reporter)
Common Name(s)		Tmc1delta;
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
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 Tmc1tm1.1Ajg 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.
Gene Symbol and Name		Tmc1, transmembrane channel-like gene family 1
Chromosome		19
Gene Common Name(s)		4933416G09Rik; Beethoven; Bth; DFNA36; DFNB11; DFNB7; RIKEN cDNA 4933416G09 gene; beethoven; deafness; dn;
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. [MGI Ref ID J:184419]

Genotyping

Genotyping Information

Genotyping Protocols

Generic LacZ Melt Curve Analysis, Melt Curve Analysis
Tmc1^tm1.1Ajg Alternate2, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Kawashima Y; Geleoc GS; Kurima K; Labay V; Lelli A; Asai Y; Makishima T; Wu DK; Della Santina CC; Holt JR; Griffith AJ. 2011. Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes. J Clin Invest 121(12):4796-809. [PubMed: 22105175]  [MGI Ref ID J:184419]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.
Mating System	Heterozygote x Heterozygote         (Female x Male)   19-APR-13
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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