Strain Name:

CBA.Cg-Tmc1dn/AjgJ

Stock Number:

006169

Availability:

Repository- Live
Homozygotes for this spontaneous mutation exhibit degeneration in the spiral ganglion neurons as well as the organ of Corti and the saccular macula. Mice are deaf throughout life. This strain may be used to research inherited deafness.

Description

Strain Information

Type Congenic; Mutant Strain; Spontaneous Mutation;
Mating SystemHomozygote x Heterozygote         (Female x Male)
Specieslaboratory mouse
Background Strain CBA/J
Donor Strain STOCK ct
H2 Haplotypek
GenerationN5+F1 (16-APR-08)
 
Donating InvestigatorDr. Andrew Griffith,   NIDCD/NIH

Appearance
agouti
Related Genotype: A/A

Development
This spontaneous mutation arose on a curly tail stock maintained by M.S. Deol and W Kocher at the MRC for Experimental Research in Inherited Diseases, University College, London in 1958. Prior to 1980, the colony was transferred to the MRC Institute of Hearing Research, Nottingham, UK and maintained as a heterogenous closed colony. Presumably in the late 1990’s, the mutation was outcrossed to CBA and transferred to Dr. Bruce Walmsley at the Australian National University in Canberra (Oleskevich S, et al. 2002). Dr. Andrew Griffith of the NIH imported the colony from Dr. Walmsley and backcrossed to CBA/J for five generations. The Jackson Laboratory Repository imported this strain in 2007.

Control Information

  Control
   000656 CBA/J
 
  Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

Related Disease (OMIM) Terms

Deafness, Autosomal Dominant Nonsyndromic Sensorineural 36; DFNA36
Deafness, Neurosensory, Autosomal Recessive 7; DFNB7

Mammalian Phenotype Terms assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Tmc1dn/Tmc1+

        involves: STOCK ct * M. m. molossinus
  • hearing/vestibular/ear phenotype
  • *normal* hearing/vestibular/ear phenotype (MGI Ref ID J:22445)
    • no abnormal ear phenotypes detected

Tmc1dn/Tmc1+

        STOCK ct/J
  • hearing/vestibular/ear phenotype
  • *normal* hearing/vestibular/ear phenotype (MGI Ref ID J:14069)
    • no abnormal ear phenotypes detected

Tmc1dn/Tmc1dn

        STOCK ct/J
  • hearing/vestibular/ear phenotype
  • abnormal ear morphology (MGI Ref ID J:1600)
    • abnormal otolith morphology (MGI Ref ID J:236)
      • in some mice, the otolith membrane degenerates completely and otoliths are lost
    • abnormal scala media morphology (MGI Ref ID J:236)
      • degeneration of most elements of the scala media complex is underway by three weeks of age
      • Dieters cell degeneration (MGI Ref ID J:236)
        • Dieters cell boundaries become indistinct and nuclei move to different levels by 10 days of age
      • abnormal stria vascularis (MGI Ref ID J:236)
        • abnormalities can be detected at 10 days of age
      • abnormal tectorial membrane morphology (MGI Ref ID J:236)
        • the free end of the membrane curls up rather than resting on hair cells by 10 days
      • organ of Corti degeneration (MGI Ref ID J:236)
        • by 9 months of age, the organ is a mass of undifferentiated cells, although the tunnel of Corti does not usually collapse
    • saccular macula degeneration (MGI Ref ID J:236)
      • some degeneration is observed in most mice
      • in severe cases, hair cells degenerate completely
  • abnormal hearing physiology (MGI Ref ID J:1600)
    • deafness (MGI Ref ID J:236)
      • mice do not respond to clicking
  • head tossing (MGI Ref ID J:236)
    • tossing movement is observed in some mice although behavior is otherwise normal
  • behavior/neurological phenotype
  • abnormal motor capabilities/coordination/movement (MGI Ref ID J:236)
    • head tossing (MGI Ref ID J:236)
      • tossing movement is observed in some mice although behavior is otherwise normal
  • nervous system phenotype
  • *normal* nervous system phenotype (MGI Ref ID J:6806)
    • no abnormal central or peripheral nervous system phenotupes detected
    • cochlear ganglion degeneration (MGI Ref ID J:236)
      • spiral ganglion degeneration begins at 50 days of age
      • by 9 months, degeneration is nearly complete

Tmc1dn/Tmc1dn

        involves: STOCK ct * M. m. molossinus
  • hearing/vestibular/ear phenotype
  • abnormal ear morphology (MGI Ref ID J:22445)
  • abnormal hearing physiology (MGI Ref ID J:22445)

Research Applications

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

Tmc1dn related

Mouse/Human Gene Homologs
deafness

Neurobiology Research
Vestibular and Hearing Defects

Sensorineural Research
Vestibular and Hearing Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol Tmc1dn
Allele Name deafness
Common Name(s) dn;
Strain of OriginSTOCK ct/J
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;
General Note The deafness mutation was found in a stock at University College, London, one of several discovered during a systematic search for uncomplicated deafness genes. Fertility of homozygotes is normal. Homozygotes are deaf their entire life, and a few of themshow slight head-tossing (J:236). Auditory thresholds of heterozygotes are normal (J:14069). Cochlear inner hair cells of Tmc1dn/Tmc1dn homozygotes are abnormally vacuolated at birth; afferent dendrites are swollen and devoid of cytoplasmic content, and an abnormal smooth endoplasmic reticulum appeared in spiral ganglion neurons. These abnormalities greatly increased by day 7, with filamentous material in the spiral ganglion neurons (J:32691). Most of the hair cells have degenerated by 40 days of age (J:22445). The macula of the sacculus may degenerate in both the head-tossing and normal behaving mice, but remains histologically normal in many of them (J:236). Webster (J:1600) found degeneration followed by partial regenerationof the organ of Corti in Tmc1dn/Tmc1dn homozygotes. Stimulus-induced action potential in the auditory nerve is absent at all ages tested from 12 days on (J:22445). However, central auditory function is preserved as shown by evokedaction potentials in the inferior colliculus in response to direct stimulation of the cochlear nerve (J:6806). Peak-to-peak response amplitudes were greater in young and intermediate aged mutant animals than in controls (J:28899). Distortion product (2f1-f2) otoacoustic emissions generated in the cochlea have been proposed as a monitor for cochlear function. In Tmc1dn/Tmc1dn mice, emissions could not be detected, as might be expected due to the considerable cochlear damage (J:32693).
Molecular Note The mutation is a 1656 bp deletion including exon 14 and flanking intronic sequences. RT-PCR analysis confirmed that an mRNA was made that spliced exon 13 sequences in frame to exon 15 sequences. [MGI Ref ID J:75142]

Genotyping

Genotyping Information

Genotyping Protocols

Tmc1dn, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Deol MS; Kocher W. 1958. A new gene for deafness in the mouse Heredity 12:463-6.  [MGI Ref ID J:236]

Additional References

Tmc1dn related

Bock GR; Frank MP; Steel KP. 1982. Preservation of central auditory function in the deafness mouse. Brain Res 239(2):608-12. [PubMed: 7093705]  [MGI Ref ID J:6806]

Horner KC; Lenoir M; Bock GR. 1985. Distortion product otoacoustic emissions in hearing-impaired mutant mice. J Acoust Soc Am 78(5):1603-11. [PubMed: 4067076]  [MGI Ref ID J:32693]

KOCHER W. 1960. [Studies on the genetics and pathology of the development of 8 labyrinth mutants (deaf-waltzer-shaker mutants) in the mouse (Mus musculus).] Z Vererbungsl 91:114-40. [PubMed: 13853422]  [MGI Ref ID J:15164]

Keats BJ; Nouri N; Huang JM; Money M; Webster DB; Berlin CI. 1995. The deafness locus (dn) maps to mouse chromosome 19. Mamm Genome 6(1):8-10. [PubMed: 7719036]  [MGI Ref ID J:22445]

Kirsch JP; Money MK; Webster DB. 1993. Mice heterozygous for the deafness gene have normal auditory thresholds. Hear Res 67(1-2):51-4. [PubMed: 8340277]  [MGI Ref ID J:14069]

Kurima K; Peters LM; Yang Y; Riazuddin S; Ahmed ZM; Naz S; Arnaud D; Drury S; Mo J; Makishima T; Ghosh M; Menon PS; Deshmukh D; Oddoux C; Ostrer H; Khan S; Riazuddin S; Deininger PL; Hampton LL; Sullivan SL; Battey JF Jr; Keats BJ; Wilcox ER; Friedman TB; Griffith AJ. 2002. Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function. Nat Genet 30(3):277-84. [PubMed: 11850618]  [MGI Ref ID J:75142]

Leao RN; Berntson A; Forsythe ID; Walmsley B. 2004. Reduced low-voltage activated K+ conductances and enhanced central excitability in a congenitally deaf (dn/dn) mouse. J Physiol 559(Pt 1):25-33. [PubMed: 15235085]  [MGI Ref ID J:105281]

Leao RN; Naves MM; Leao KE; Walmsley B. 2006. Altered sodium currents in auditory neurons of congenitally deaf mice. Eur J Neurosci 24(4):1137-46. [PubMed: 16930439]  [MGI Ref ID J:112908]

Leao RN; Svahn K; Berntson A; Walmsley B. 2005. Hyperpolarization-activated (I) currents in auditory brainstem neurons of normal and congenitally deaf mice. Eur J Neurosci 22(1):147-57. [PubMed: 16029204]  [MGI Ref ID J:101088]

Marcotti W; Erven A; Johnson SL; Steel KP; Kros CJ. 2006. Tmc1 is necessary for normal functional maturation and survival of inner and outer hair cells in the mouse cochlea. J Physiol 574(Pt 3):677-98. [PubMed: 16627570]  [MGI Ref ID J:134124]

McKay SM; Oleskevich S. 2007. The role of spontaneous activity in development of the endbulb of Held synapse. Hear Res 230(1-2):53-63. [PubMed: 17590547]  [MGI Ref ID J:123325]

Oleskevich S; Walmsley B. 2002. Synaptic transmission in the auditory brainstem of normal and congenitally deaf mice. J Physiol 540(Pt 2):447-55. [PubMed: 11956335]  [MGI Ref ID J:105943]

Oleskevich S; Youssoufian M; Walmsley B. 2004. Presynaptic plasticity at two giant auditory synapses in normal and deaf mice. J Physiol 560(Pt 3):709-19. [PubMed: 15331689]  [MGI Ref ID J:105517]

Pujol R; Shnerson A; Lenoir M; Deol MS. 1983. Early degeneration of sensory and ganglion cells in the inner ear of mice with uncomplicated genetic deafness (dn): preliminary observations. Hear Res 12(1):57-63. [PubMed: 6662828]  [MGI Ref ID J:32691]

Steel KP; Bock GR. 1984. Electrically-evoked responses in animals with progressive spiral ganglion degeneration. Hear Res 15(1):59-67. [PubMed: 6541219]  [MGI Ref ID J:28899]

Steel KP; Bock GR. 1980. The nature of inherited deafness in deafness mice. Nature 288(5787):159-61. [PubMed: 7432512]  [MGI Ref ID J:6409]

Webster DB. 1992. Degeneration followed by partial regeneration of the organ of Corti in deafness (dn/dn) mice. Exp Neurol 115(1):27-31. [PubMed: 1728569]  [MGI Ref ID J:1600]

Youssoufian M; Oleskevich S; Walmsley B. 2005. Development of a robust central auditory synapse in congenital deafness. J Neurophysiol 94(5):3168-80. [PubMed: 16000524]  [MGI Ref ID J:116868]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations             View   International   Pricing
Weeks of AgePrice*GenderGenotypes Provided
Individual Mouse Price $236.40Female or MaleHeterozygous for Tmc1dn
$291.90Female or MaleHomozygous for Tmc1dn
Pairs /Price*Pair Genotype
$528.30Heterozygous for Tmc1dn x Homozygous for Tmc1dn
$528.30Homozygous for Tmc1dn x Heterozygous for Tmc1dn
*Price(s) in US dollars ($)

Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes

Pricing for International shipping destinations             View   USA, Canada and Mexico   Pricing
Weeks of AgePrice*GenderGenotypes Provided
Individual Mouse Price $307.40Female or MaleHeterozygous for Tmc1dn
$379.50Female or MaleHomozygous for Tmc1dn
Pairs /Price*Pair Genotype
$686.80Heterozygous for Tmc1dn x Homozygous for Tmc1dn
$686.80Homozygous for Tmc1dn x Heterozygous for Tmc1dn
*Price(s) in US dollars ($)

Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes

Control Information

  Control
   000656 CBA/J
 
  Considerations for Choosing Controls
  USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
  International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

View JAX® Mice & Services Conditions of Use.

The Jackson Laboratory's Genotype Promise

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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