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-Accn3tm1Wsh/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. Species laboratory mouse Generation N10pN1 Generation Definitions   Donating Investigator Michael Welsh,   University of Iowa

Description
Homozygous Asic3 (amiloride-sensitive cation channel 3) targeted mutation mice display alterations in normal and pain-associated cutaneous mechanosensitivity and inflammatory pain sensation, visual loss associated with night blindness, and age-induced hearing loss. Mice show increased sensitivity of mechanoreceptors detecting light touch. Sensitivity of mechanoreceptors responding to noxious pinch is decreased as is the response of acid- and noxious heat-sensitive nociceptors. No mRNA is detectable by RT-PCR in the dorsal root ganglion. Protein is not found in trigeminal and dorsal root ganglion. This strain may be useful in further elucidating the role of this gene in mechanosensation.

Development
A region of the targeted gene containing the first exon (which includes the start ATG codon), the first transmembrane segment and part of the extracellular domain, was replaced with a loxP-flanked 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 10 generations by the donating laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Asic3

012880	B6.Cg-Tg(Syn1-Accn3*)30795-2Wsh/J
012879	B6.Cg-Tg(Syn1-Accn3*)30795-3Wsh/J

View Strains carrying other alleles of Asic3     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Asic3^tm1Wsh/Asic3^tm1Wsh

        B6.129-Asic3^tm1Wsh

• behavior/neurological phenotype
• abnormal mechanical nociception
  • following induction of colonic distention, mice fail to exhibit zymogen-induced behavioral hypersensitivity, as measured by visceral nociception, unlike similarly treated wild-type mice   (MGI Ref ID J:128319)
• homeostasis/metabolism phenotype
• abnormal physiological response to xenobiotic
  • following induction of colonic distention, mice fail to exhibit zymogen-induced behavioral hypersensitivity, as measured by visceral nociception, unlike similarly treated wild-type mice   (MGI Ref ID J:128319)
• integument phenotype
• abnormal mechanical nociception
  • following induction of colonic distention, mice fail to exhibit zymogen-induced behavioral hypersensitivity, as measured by visceral nociception, unlike similarly treated wild-type mice   (MGI Ref ID J:128319)

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

Asic3^tm1Wsh/Asic3^tm1Wsh

        involves: 129S1/Sv * 129X1/SvJ * C57BL

• behavior/neurological phenotype
• hyperalgesia
  • at site of injury (carrageenan-induced inflammation), mice showed increased sensitivity to mechanical stimuli, but not to noxious thermal stimulus   (MGI Ref ID J:73505)
  • responses to somatosensory stimuli under normal conditions were similar to wild-type littermates   (MGI Ref ID J:73505)
• hearing/vestibular/ear phenotype
• increased or absent threshold for auditory brainstem response
  • at 2 months, homozygotes display no vestibular phenotype (such as head tossing, circling or hyperactivity) and no significant differences in the latency, form or sensitivity of ABR thresholds relative to wild-type mice   (MGI Ref ID J:89141)
  • at 2 and 4 months, homozygotes show an ABR threshold of 47 dB and 68 dB, respectively, whereas wild-type thresholds are 42 dB at both ages   (MGI Ref ID J:89141)
  • at 6 months or later, homozygotes continue to display an elevation of 20 dB or higher in ABR thresholds relative to wild-type   (MGI Ref ID J:89141)
  • however, no significant differences in ABR thresholds are noted between wild-type and mutant mice at 10 months   (MGI Ref ID J:89141)
• integument phenotype
• hyperalgesia
  • at site of injury (carrageenan-induced inflammation), mice showed increased sensitivity to mechanical stimuli, but not to noxious thermal stimulus   (MGI Ref ID J:73505)
  • responses to somatosensory stimuli under normal conditions were similar to wild-type littermates   (MGI Ref ID J:73505)

Asic3^tm1Wsh/Asic3^tm1Wsh

        involves: 129S1/Sv * 129X1/SvJ

• behavior/neurological phenotype
• hyporesponsive to tactile stimuli
  • following a second injection of pH 4 saline 5 days after the first injection, mice fail to exhibit induction of mechanical hyperalgesia unlike wild-type mice   (MGI Ref ID J:119060)
  • after a second pH 4 saline, spinal wide dynamic range (WDR) neuron response fail exhibit expansion of the receptive to tactile stimuli unlike wild-type neurons   (MGI Ref ID J:119060)
• nervous system phenotype
• abnormal nervous system electrophysiology
  • following a second injection of pH 4 saline 5 days after the first injection, mice fail to exhibit induction of mechanical hyperalgesia unlike wild-type mice   (MGI Ref ID J:119060)
  • after a second pH 4 saline, spinal wide dynamic range (WDR) neuron response fail exhibit expansion of the receptive to tactile stimuli unlike wild-type neurons   (MGI Ref ID J:119060)
• integument phenotype
• hyporesponsive to tactile stimuli
  • following a second injection of pH 4 saline 5 days after the first injection, mice fail to exhibit induction of mechanical hyperalgesia unlike wild-type mice   (MGI Ref ID J:119060)
  • after a second pH 4 saline, spinal wide dynamic range (WDR) neuron response fail exhibit expansion of the receptive to tactile stimuli unlike wild-type neurons   (MGI Ref ID J:119060)

View Research Applications

Research Applications

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

Sensorineural Research
Eye Defects
Hearing Defects
      Age related hearing loss
Nociception

Asic3^tm1Wsh related

Neurobiology Research

Sensorineural Research
Hearing Defects
Nociception

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Asic3tm1Wsh
Allele Name		targeted mutation 1, Michael J Welsh
Allele Type		Targeted (knock-out)
Common Name(s)		ASIC3-; DRASIC-;
Mutation Made By		Maggie Price,   University of Iowa
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Asic3, acid-sensing (proton-gated) ion channel 3
Chromosome		5
Gene Common Name(s)		ACCN3; AW742291; Accn3; DRASIC; SLNAC1; TNaC1; amiloride-sensitive cation channel 3; expressed sequence AW742291;
Molecular Note		Exon 1 was replaced with a floxed neomycin selection cassette inserted by homologous recombination. The deleted region contained the translational start codon and encoded the transmembrane domain and a portion of the extracellular domain. Transcript was undetected in homozygous mutant mice by RT-PCR analysis. [MGI Ref ID J:73505]

Genotyping

Genotyping Information

Genotyping Protocols

Accn3^tm1Wsh, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Price MP; McIlwrath SL; Xie J; Cheng C; Qiao J; Tarr DE; Sluka KA; Brennan TJ; Lewin GR; Welsh MJ. 2001. The DRASIC Cation Channel Contributes to the Detection of Cutaneous Touch and Acid Stimuli in Mice. Neuron 32(6):1071-83. [PubMed: 11754838]  [MGI Ref ID J:73505]

Additional References

Asic3^tm1Wsh related

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]

Bielefeldt K; Davis BM. 2008. Differential effects of ASIC3 and TRPV1 deletion on gastroesophageal sensation in mice. Am J Physiol Gastrointest Liver Physiol 294(1):G130-8. [PubMed: 17975130]  [MGI Ref ID J:130510]

Burnes LA; Kolker SJ; Danielson JF; Walder RY; Sluka KA. 2008. Enhanced muscle fatigue occurs in male but not female ASIC3-/- mice. Am J Physiol Regul Integr Comp Physiol 294(4):R1347-55. [PubMed: 18305024]  [MGI Ref ID J:133223]

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]

Hildebrand MS; de Silva MG; Klockars T; Rose E; Price M; Smith RJ; McGuirt WT; Christopoulos H; Petit C; Dahl HH. 2004. Characterisation of DRASIC in the mouse inner ear. Hear Res 190(1-2):149-60. [PubMed: 15051137]  [MGI Ref ID J:89141]

Jones RC 3rd; Otsuka E; Wagstrom E; Jensen CS; Price MP; Gebhart GF. 2007. Short-term sensitization of colon mechanoreceptors is associated with long-term hypersensitivity to colon distention in the mouse. Gastroenterology 133(1):184-94. [PubMed: 17553498]  [MGI Ref ID J:128319]

Jones RC 3rd; Xu L; Gebhart GF. 2005. The mechanosensitivity of mouse colon afferent fibers and their sensitization by inflammatory mediators require transient receptor potential vanilloid 1 and acid-sensing ion channel 3. J Neurosci 25(47):10981-9. [PubMed: 16306411]  [MGI Ref ID J:103423]

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]

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]

Sluka KA; Radhakrishnan R; Benson CJ; Eshcol JO; Price MP; Babinski K; Audette KM; Yeomans DC; Wilson SP. 2007. ASIC3 in muscle mediates mechanical, but not heat, hyperalgesia associated with muscle inflammation. Pain 129(1-2):102-12. [PubMed: 17134831]  [MGI Ref ID J:129598]

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 maintained as a live colony, homozygotes or heterozygotes may be bred.

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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