Strain Name:

CBACaJ;129S-Chrna9tm1Bedv/J

Stock Number:

005696

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Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names CBACaJ;129S-Chrna9tm1Jbdv/J    (Changed: 30-SEP-05 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
Generation?+N1p (05-FEB-06)
Generation Definitions
 
Donating Investigator Douglas Vetter,   Tufts University School of Medicine

Description
Mice homozygous for the targeted mutation are viable and fertile and have normal balance, movement, cochlear duct morphology, and gross development and position of the olivo-cochlear (OC) bundle. However, most outer hair cells are innervated by one large OC efferent fiber terminal instead of multiple smaller terminals as in wildtype. OC terminal plexus in close apposition to the inner hair somata are absent in homozygotes. Null mice fail to show electrophysiological cochlear responses during efferent fiber activation. This mutant may be suitable for use in studies related to auditory-related studies of the inner ear, including the cochlea, organ of Corti, and hair cells as well as acetylcholine receptor/neurotransmitter or olfactory research.

Development
A targeting vector containing a neomycin resistance gene was used to replace the targeted gene's fourth exon and the flanking intronic sequences. The fourth exon codes for the ligand binding site, the entire first and second transmembrane domains, including the pore region, and a portion of the third transmembrane domain. The construct was electroporated into 129S1/Sv-derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and chimeric males were mated to CBA/CaJ females. Mutant mice were progressively backcrossed to wildtype CBA/CaJ for 7 generations. This mutant was then bred to mice with the same mutation on a 129S6/SvEvTac and/or mixed (CBA/CaJ x 129S6/SvEvTac) background for an unknown number of generations to rescue the line. The rescued line was then maintained by sibling crosses before arrival at The Jackson Laboratory. Upon arrival, the mutant mice were crossed once to CBA/CaJ (Stock No. 000654) before being made homozygous.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Chrna9tm1Bedv/Chrna9tm1Bedv

        either: CB.129S1-Chrna9tm1Bedv or (involves: 129S1/Sv) or (involves: 129S1/Sv * CBA/CaJ)
  • hearing/vestibular/ear phenotype
  • *normal* hearing/vestibular/ear phenotype
    • homozygotes are viable with a normal Preyer's reflex and no gross deficits in balance or movement   (MGI Ref ID J:55406)
    • no structural abnormalities in cochlear hair cells, supporting cells or spiral ganglion neurons are observed   (MGI Ref ID J:55406)
    • in addition, development and position of the olivocochlear bundle remains unchanged   (MGI Ref ID J:55406)
    • in vitro, mutant apical OHCs exhibit normal electromotility in response to a 100-Hz sinusoidal voltage command relative to wild-type OHCs   (MGI Ref ID J:100073)
    • abnormal cochlear IHC efferent innervation pattern
      • unlike wild-type mice, homozygotes appear to lack a sparse plexus of efferent terminals in close apposition to the IHC somata   (MGI Ref ID J:55406)
      • however, a dense plexus of terminals is still present below the IHCs   (MGI Ref ID J:55406)
    • abnormal cochlear OHC efferent innervation pattern
      • most efferent terminals under mutant OHCs occur as large singlets rather than as clusters of roughly equal-size terminals   (MGI Ref ID J:55406)
      • most mutant OHCs are contacted by only one terminal (66.7%) and very few by >2 terminals, whereas 61.8% of wild-type OHCs are contacted by two terminals   (MGI Ref ID J:55406)
    • abnormal cochlear nerve compound action potential
      • at 6-24 weeks, homozygotes fail to show suppression of compound action potential (CAP) amplitudes during efferent fiber activation by olivocochlear (OC) shocks   (MGI Ref ID J:55406)
      • however, in the absence of crossing OC bundle electrical stimulation, homozygotes display normal CAP thresholds at 16 kHz relative to wild-type mice   (MGI Ref ID J:55406)
      • also, at 4-9 weeks, homozygotes show normal mean CAP threshold curves over the entire range of mouse hearing (between 1.7 and 50 kHz) relative to 129S6/SvEvTac control mice   (MGI Ref ID J:100073)
    • abnormal distortion product otoacoustic emission
      • homozygotes fail to show suppression of distortion product otoacoustic emissions (DPOAEs) during efferent fiber activation by olivocochlear (OC) shocks   (MGI Ref ID J:55406)
      • however, in the absence of OC bundle electrical stimulation, homozygotes display normal DPOAEs relative to wild-type mice   (MGI Ref ID J:55406)
  • nervous system phenotype
  • abnormal cochlear nerve compound action potential
    • at 6-24 weeks, homozygotes fail to show suppression of compound action potential (CAP) amplitudes during efferent fiber activation by olivocochlear (OC) shocks   (MGI Ref ID J:55406)
    • however, in the absence of crossing OC bundle electrical stimulation, homozygotes display normal CAP thresholds at 16 kHz relative to wild-type mice   (MGI Ref ID J:55406)
    • also, at 4-9 weeks, homozygotes show normal mean CAP threshold curves over the entire range of mouse hearing (between 1.7 and 50 kHz) relative to 129S6/SvEvTac control mice   (MGI Ref ID J:100073)
  • abnormal sensory neuron innervation pattern
    • at 6-24 weeks, homozygotes exhibit abnormal efferent innervation in both OHC and IHC regions of the cochlea   (MGI Ref ID J:55406)
    • abnormal cochlear IHC efferent innervation pattern
      • unlike wild-type mice, homozygotes appear to lack a sparse plexus of efferent terminals in close apposition to the IHC somata   (MGI Ref ID J:55406)
      • however, a dense plexus of terminals is still present below the IHCs   (MGI Ref ID J:55406)
    • abnormal cochlear OHC efferent innervation pattern
      • most efferent terminals under mutant OHCs occur as large singlets rather than as clusters of roughly equal-size terminals   (MGI Ref ID J:55406)
      • most mutant OHCs are contacted by only one terminal (66.7%) and very few by >2 terminals, whereas 61.8% of wild-type OHCs are contacted by two terminals   (MGI Ref ID J:55406)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Chrna9tm1Bedv/Chrna9tm1Bedv

        Background Not Specified
  • hearing/vestibular/ear phenotype
  • abnormal cochlear outer hair cell physiology
    • small inward currents are detected when both KCl and acetylcholinesterase are applied; nicotine did not evoke currents in OHCs that were responsive to ACh   (MGI Ref ID J:130585)
  • nervous system phenotype
  • abnormal cochlear outer hair cell physiology
    • small inward currents are detected when both KCl and acetylcholinesterase are applied; nicotine did not evoke currents in OHCs that were responsive to ACh   (MGI Ref ID J:130585)
View Research Applications

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

Neurobiology Research
Channel and Transporter Defects
      sodium/potassium
Hearing Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects
Receptor Defects
      cholinergic receptor

Sensorineural Research
Hearing Defects

Chrna9tm1Bedv related

Neurobiology Research
Channel and Transporter Defects
      sodium/potassium
Hearing Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects
Receptor Defects
      cholinergic receptor

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Chrna9tm1Bedv
Allele Name targeted mutation 1, Belen Elgoyhen and Douglas E Vetter
Allele Type Targeted (Null/Knockout)
Common Name(s) Chrna9tm1Jbdv; alpha9 knockout; alpha9-;
Mutation Made By Douglas Vetter,   Tufts University School of Medicine
Strain of Origin129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line NameW9.5/W95
ES Cell Line Strain129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name Chrna9, cholinergic receptor, nicotinic, alpha polypeptide 9
Chromosome 5
Gene Common Name(s) 2410015I05Rik; Acra9; EG666827; Gm8311; HSA243342; NACHRA9; RIKEN cDNA 2410015I05 gene; acetylcholine receptor alpha 9; predicted gene 8311; predicted gene, EG666827;
Molecular Note Exon 4 and flanking intronic sequences were replaced with a neomycin selection cassette. The deleted sequences encode the ligand-binding site and the first two transmembrane domains. RT-PCR analysis on nasal epithelium derived from homozygous mice confirmed that no detectable transcript containg sequences from exon 4 is produced from this allele. [MGI Ref ID J:55406]

Genotyping

Genotyping Information

Genotyping Protocols

Chrna9tm1Bedv, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Vetter DE; Liberman MC; Mann J; Barhanin J; Boulter J; Brown MC; Saffiote-Kolman J; Heinemann SF; Elgoyhen AB. 1999. Role of alpha9 nicotinic ACh receptor subunits in the development and function of cochlear efferent innervation. Neuron 23(1):93-103. [PubMed: 10402196]  [MGI Ref ID J:55406]

Additional References

Chrna9tm1Bedv related

Fuchs PA; Lehar M; Hiel H. 2014. Ultrastructure of cisternal synapses on outer hair cells of the mouse cochlea. J Comp Neurol 522(3):717-29. [PubMed: 24122766]  [MGI Ref ID J:206606]

He DZ; Cheatham MA; Pearce M; Vetter DE. 2004. Mouse outer hair cells lacking the alpha9 ACh receptor are motile. Brain Res Dev Brain Res 148(1):19-25. [PubMed: 14757515]  [MGI Ref ID J:100073]

Maison SF; Vetter DE; Liberman MC. 2007. A novel effect of cochlear efferents: in vivo response enhancement does not require alpha9 cholinergic receptors. J Neurophysiol 97(5):3269-78. [PubMed: 17344378]  [MGI Ref ID J:150250]

May BJ; Prosen CA; Weiss D; Vetter D. 2002. Behavioral investigation of some possible effects of the central olivocochlear pathways in transgenic mice. Hear Res 171(1-2):142-157. [PubMed: 12204358]  [MGI Ref ID J:100074]

Prosen CA; Bath KG; Vetter DE; May BJ. 2000. Behavioral assessments of auditory sensitivity in transgenic mice J Neurosci Methods 97(1):59-67. [PubMed: 10771076]  [MGI Ref ID J:62359]

Turcan S; Slonim DK; Vetter DE. 2010. Lack of nAChR activity depresses cochlear maturation and up-regulates GABA system components: temporal profiling of gene expression in alpha9 null mice. PLoS One 5(2):e9058. [PubMed: 20140217]  [MGI Ref ID J:158009]

Vetter DE; Katz E; Maison SF; Taranda J; Turcan S; Ballestero J; Liberman MC; Elgoyhen AB; Boulter J. 2007. The alpha10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system. Proc Natl Acad Sci U S A 104(51):20594-9. [PubMed: 18077337]  [MGI Ref ID J:130585]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice are bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $1650.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $2145.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
 
  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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