Strain Name:

B6.129-Asic2tm1Wsh/J

Stock Number:

013126

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Homozygous Asic2 knockout mice display subtle alterations in mechanoreceptor and spiral ganglion function, and are more sensitive to light-induced retinal degeneration. This strain may be helpful in studies of touch sensation.

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 B6.129-Accn1tm1Wsh/J    (Changed: 05-DEC-12 )
Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
GenerationN10pN1
Generation Definitions
 
Donating Investigator Michael Welsh,   University of Iowa

Description
Homozygous Asic2 (amiloride-sensitive cation channel 1, neuronal (degenerin)) targeted mutation mice display subtle alterations in mechanoreceptor and spiral ganglion function, and are more sensitive to light-induced retinal degeneration. Transcripts and protein are missing for both spliced forms of the gene, as determined by Western and Northern blot analysis of mouse brain. Homozygous mice show a reduced reproductive capacity that is reportedly 25% that of wild-type mice. This strain may be helpful in studies of touch sensation.

Development
Exons 8, 9, and flanking intronic sequences were replaced with a neomycin resistance cassette in (129X1/SvJ x 129S1/Sv)F1- Kitl+-derived R1 embryonic stem (ES) cells. This strain was backcrossed to C57BL/6 for more than ten generations by the donating laboratory.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Asic2
012877   B6.Cg-Tg(Syn1-Accn1)32843-3Wsh/J
012878   B6.Cg-Tg(Syn1-Accn1)32851-3Wsh/J
View Strains carrying other alleles of Asic2     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Asic2tm1Wsh/Asic2+

        involves: 129S1/Sv * 129X1/SvJ
  • cardiovascular system phenotype
  • abnormal blood vessel physiology
    • wall tension under calcium ion containing conditions in cerebral arteries is increased compared to in wild-type mice   (MGI Ref ID J:135644)
    • however, mechanical properties of blood vessels (strain, stress, stress-strain relationship, incremental distensibility, inner diameter, outer diameter, wall thickness, and wall thickness-to-lumen ratio)   (MGI Ref ID J:135644)
    • decreased vasoconstriction
      • mice fail to exhibit pressure-induced constriction in the middle cerebral artery in the presence of calcium unlike similarly treated wild-type mice   (MGI Ref ID J:135644)
      • mice fail to generate myogenic tone in response to intraluminal pressure unlike similarly treated wild-type mice   (MGI Ref ID J:135644)
  • muscle phenotype
  • decreased vasoconstriction
    • mice fail to exhibit pressure-induced constriction in the middle cerebral artery in the presence of calcium unlike similarly treated wild-type mice   (MGI Ref ID J:135644)
    • mice fail to generate myogenic tone in response to intraluminal pressure unlike similarly treated wild-type mice   (MGI Ref ID J:135644)

Asic2tm1Wsh/Asic2tm1Wsh

        involves: 129S1/Sv * 129X1/SvJ
  • nervous system phenotype
  • abnormal nervous system electrophysiology
    • low threshold, rapid adapting mechanoreceptors exhibit reduced sensitivity compared with wild-type mechanoreceptors   (MGI Ref ID J:76712)
    • low threshold, rapid adapting mechanoreceptor stimulus response function exhibits reduced discharge frequency and flattens unlike in wild-type mechanoreceptors   (MGI Ref ID J:76712)
    • low threshold, rapid adapting mechanoreceptors exhibit reduced sensitivity between 5 and 20 um displacement unlike wild-type mechanoreceptor   (MGI Ref ID J:76712)
    • the stimulus-response of slowly adapting mechanoreceptor exhibits decreased sensitivity compared to wild-type mechanoreceptors   (MGI Ref ID J:76712)
    • however, sensory neurons exhibit normal response to current injection   (MGI Ref ID J:76712)
  • hearing/vestibular/ear phenotype
  • abnormal hearing electrophysiology
    • pH changes fail to generate firing of action potentials in spiral ganglion unlike similarly treated wild-type cells   (MGI Ref ID J:96521)
    • proton-induced current flows in spiral ganglion compared with wild-type cells   (MGI Ref ID J:96521)
    • following exposure to 110 dB white-band noise, mice exhibit a decrease in their susceptibilities to noise-induced temporary threshold shifts compared with wild-type mice   (MGI Ref ID J:96521)
    • however, auditory brainstem response is normal   (MGI Ref ID J:96521)
  • cardiovascular system phenotype
  • decreased vasoconstriction
    • mice exhibit decreased pressure-induced constriction of the middle cerebral artery in the presence of calcium unlike similarly treated wild-type mice   (MGI Ref ID J:135644)
    • mice develop myogenic tone with increases in intraluminal pressure but generate less tone at every pressure step compared with similarly treated wild-type mice   (MGI Ref ID J:135644)
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • hyperalgesia induced by repeated acid injections is normal   (MGI Ref ID J:119060)
  • taste/olfaction phenotype
  • *normal* taste/olfaction phenotype
    • mice exhibit normal physiological responses to acid taste stimuli   (MGI Ref ID J:96875)
  • muscle phenotype
  • decreased vasoconstriction
    • mice exhibit decreased pressure-induced constriction of the middle cerebral artery in the presence of calcium unlike similarly treated wild-type mice   (MGI Ref ID J:135644)
    • mice develop myogenic tone with increases in intraluminal pressure but generate less tone at every pressure step compared with similarly treated wild-type mice   (MGI Ref ID J:135644)
View Research Applications

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

Neurobiology Research
Channel and Transporter Defects

Sensorineural Research
Retinal Degeneration

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Asic2tm1Wsh
Allele Name targeted mutation 1, Michael J Welsh
Allele Type Targeted (Null/Knockout)
Common Name(s) ASIC2-; BNC1-;
Mutation Made By Maggie Price,   University of Iowa
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Asic2, acid-sensing (proton-gated) ion channel 2
Chromosome 11
Gene Common Name(s) ACCN; ACCN1; ASIC2a; Accn1; BNC1; BNC1k; BNaC1; BNaC1a; MDEG; MDEG1; MDEG2; amiloride-sensitive cation channel 1, neuronal (degenerin); hBNaC1;
Molecular Note A neomycin cassette was inserted to disrupt two exons encoding the second transmembrane domain, which is common to both splice variants, as well as a channel pore. Transcripts were not detected in the brains of homozygous mutant mice. Neither in situ hybridization nor immunostaining detected protein in the large or small dorsal root ganglion neurons of homozygous animals. [MGI Ref ID J:76712]

Genotyping

Genotyping Information

Genotyping Protocols

Accn1tm1Wsh, Standard PCR
Accn1tm1Wsh, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Asic2tm1Wsh related

Askwith CC; Wemmie JA; Price MP; Rokhlina T; Welsh MJ. 2004. Acid-sensing ion channel 2 (ASIC2) modulates ASIC1 H+-activated currents in hippocampal neurons. J Biol Chem 279(18):18296-305. [PubMed: 14960591]  [MGI Ref ID J:124264]

Benson CJ; Xie J; Wemmie JA; Price MP; Henss JM; Welsh MJ; Snyder PM. 2002. Heteromultimers of DEG/ENaC subunits form H+-gated channels in mouse sensory neurons. Proc Natl Acad Sci U S A 99(4):2338-43. [PubMed: 11854527]  [MGI Ref ID J:74681]

Cho JH; Askwith CC. 2008. Presynaptic release probability is increased in hippocampal neurons from ASIC1 knockout mice. J Neurophysiol 99(2):426-41. [PubMed: 18094106]  [MGI Ref ID J:147665]

Chu XP; Wemmie JA; Wang WZ; Zhu XM; Saugstad JA; Price MP; Simon RP; Xiong ZG. 2004. Subunit-dependent high-affinity zinc inhibition of acid-sensing ion channels. J Neurosci 24(40):8678-89. [PubMed: 15470133]  [MGI Ref ID J:109770]

Drew LJ; Rohrer DK; Price MP; Blaver KE; Cockayne DA; Cesare P; Wood JN. 2004. Acid-sensing ion channels ASIC2 and ASIC3 do not contribute to mechanically activated currents in mammalian sensory neurones. J Physiol 556(Pt 3):691-710. [PubMed: 14990679]  [MGI Ref ID J:105518]

Du J; Reznikov LR; Price MP; Zha XM; Lu Y; Moninger TO; Wemmie JA; Welsh MJ. 2014. Protons are a neurotransmitter that regulates synaptic plasticity in the lateral amygdala. Proc Natl Acad Sci U S A 111(24):8961-6. [PubMed: 24889629]  [MGI Ref ID J:211633]

Gannon KP; Vanlandingham LG; Jernigan NL; Grifoni SC; Hamilton G; Drummond HA. 2008. Impaired pressure-induced constriction in mouse middle cerebral arteries of ASIC2 knockout mice. Am J Physiol Heart Circ Physiol 294(4):H1793-803. [PubMed: 18296560]  [MGI Ref ID J:135644]

Hattori T; Chen J; Harding AM; Price MP; Lu Y; Abboud FM; Benson CJ. 2009. ASIC2a and ASIC3 heteromultimerize to form pH-sensitive channels in mouse cardiac dorsal root ganglia neurons. Circ Res 105(3):279-86. [PubMed: 19590043]  [MGI Ref ID J:164935]

Jiang Q; Li MH; Papasian CJ; Branigan D; Xiong ZG; Wang JQ; Chu XP. 2009. Characterization of acid-sensing ion channels in medium spiny neurons of mouse striatum. Neuroscience 162(1):55-66. [PubMed: 19376200]  [MGI Ref ID J:152937]

Jiang Q; Wang CM; Fibuch EE; Wang JQ; Chu XP. 2013. Differential regulation of locomotor activity to acute and chronic cocaine administration by acid-sensing ion channel 1a and 2 in adult mice. Neuroscience 246:170-8. [PubMed: 23644053]  [MGI Ref ID J:201444]

Jing L; Jiang YQ; Jiang Q; Wang B; Chu XP; Zha XM. 2011. The interaction between the first transmembrane domain and the thumb of ASIC1a is critical for its N-glycosylation and trafficking. PLoS One 6(10):e26909. [PubMed: 22046405]  [MGI Ref ID J:179705]

Lu Y; Ma X; Sabharwal R; Snitsarev V; Morgan D; Rahmouni K; Drummond HA; Whiteis CA; Costa V; Price M; Benson C; Welsh MJ; Chapleau MW; Abboud FM. 2009. The ion channel ASIC2 is required for baroreceptor and autonomic control of the circulation. Neuron 64(6):885-97. [PubMed: 20064394]  [MGI Ref ID J:157720]

Page AJ; Brierley SM; Martin CM; Price MP; Symonds E; Butler R; Wemmie JA; Blackshaw LA. 2005. Different contributions of ASIC channels 1a, 2, and 3 in gastrointestinal mechanosensory function. Gut 54(10):1408-15. [PubMed: 15987792]  [MGI Ref ID J:194728]

Peng BG; Ahmad S; Chen S; Chen P; Price MP; Lin X. 2004. Acid-sensing ion channel 2 contributes a major component to acid-evoked excitatory responses in spiral ganglion neurons and plays a role in noise susceptibility of mice. J Neurosci 24(45):10167-75. [PubMed: 15537887]  [MGI Ref ID J:96521]

Petroff E; Snitsarev V; Gong H; Abboud FM. 2012. Acid sensing ion channels regulate neuronal excitability by inhibiting BK potassium channels. Biochem Biophys Res Commun 426(4):511-5. [PubMed: 22960074]  [MGI Ref ID J:190140]

Price MP; Lewin GR; McIlwrath SL; Cheng C; Xie J; Heppenstall PA; Stucky CL; Mannsfeldt AG; Brennan TJ; Drummond HA; Qiao J; Benson CJ; Tarr DE; Hrstka RF; Yang B; Williamson RA; Welsh MJ. 2000. The mammalian sodium channel BNC1 is required for normal touch sensation. Nature 407(6807):1007-11. [PubMed: 11069180]  [MGI Ref ID J:76712]

Richter TA; Dvoryanchikov GA; Roper SD; Chaudhari N. 2004. Acid-sensing ion channel-2 is not necessary for sour taste in mice. J Neurosci 24(16):4088-91. [PubMed: 15102924]  [MGI Ref ID J:96875]

Santos-Torres J; Slimak MA; Auer S; Ibanez-Tallon I. 2011. Cross-reactivity of acid-sensing ion channel and Na(+)-H(+) exchanger antagonists with nicotinic acetylcholine receptors. J Physiol 589(Pt 21):5109-23. [PubMed: 21911609]  [MGI Ref ID J:191550]

Sluka KA; Price MP; Breese NM; Stucky CL; Wemmie JA; Welsh MJ. 2003. Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1. Pain 106(3):229-39. [PubMed: 14659506]  [MGI Ref ID J:119060]

Zha XM; Costa V; Harding AM; Reznikov L; Benson CJ; Welsh MJ. 2009. ASIC2 subunits target acid-sensing ion channels to the synapse via an association with PSD-95. J Neurosci 29(26):8438-46. [PubMed: 19571134]  [MGI Ref ID J:150806]

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 maintained as a live colony, heterozygotes or homozygotes may be bred. Homozygous mice show a reduced reproductive capacity that is reportedly 25% that of wildtype mice.

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* $2140.00
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.

Standard Supply

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

Supply Notes

  • 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* $2782.00
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.

Standard Supply

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

Supply Notes

  • 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
   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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