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. Species laboratory 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

Chrna9^tm1Bedv/Chrna9^tm1Bedv

        either: CB.129S1-Chrna9^tm1Bedv 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 may relate to a genetic background differing from this JAX^® Mice strain.

Chrna9^tm1Bedv/Chrna9^tm1Bedv

        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

Chrna9^tm1Bedv 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 (knock-out)
Common Name(s)		Chrna9tm1Jbdv; alpha9 knockout; alpha9-;
Mutation Made By		Douglas Vetter,   Tufts University School of Medicine
Strain of Origin		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line Name		W9.5/W95
ES Cell Line Strain		129S1/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

Chrna9^tm1Bedv, 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

Chrna9^tm1Bedv related

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 & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

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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