Description

Strain Information

Type Coisogenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Heterozygote         (Female x Male) Mating System Heterozygote x Homozygote         (Female x Male) Species laboratory mouse Generation pN1F23+22N1F3 (06-DEC-07)

Appearance
agouti, ataxic
Related Genotype: A/A Atp2b2^dfw/Atp2b2^dfw

agouti, unaffected
Related Genotype: A/A Atp2b2^dfw/+

Important Note
This strain may carry a chromosomal inversion on Chromosome 6 (see C3H/HeJ, Stock No. 000659).

Description
Mice homozygous for the deaf waddler spontaneous mutation (Atp2b2^dfw) are deaf, walk with a hesitant, wobbly gait, and bob their heads. Both sexes are fertile.

Development
The mutation deaf waddler (Atp2b2^dfw) arose spontaneously at The Jackson Laboratory in 1979 in the strain C3H/HeJ when that inbred was at F160. This mutant sub-line was bred to homozygosity and maintained by sibling mating homozgyotes until F12 when a homozygous male was backcrossed to a C3H/HeJ female. The strain was then maintained by sibling mating with forced heterozygosity. It was cryopreserved beginning in 1991 from the breeding of heterozygotes and homozygotes, with the females at generation F24 to F30 and the males at generation F23 to F25.

Control Information

	Control
	Heterozygote from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Atp2b2

003892	B6;BKS-Atp2b2dfw-3J/J
002894	CByJ.A-Atp2b2dfw-2J/J

View Strains carrying other alleles of Atp2b2     (2 strains)

Additional Web Information

JAX^® NOTES, Fall 2003; 491. Chromosomal Inversion Discovered in C3H/HeJ Mice.
JAX^® NOTES, Spring 2005; 497. Update of Chromosome 6 Inversion in JAX^® Mice Strain C3H/HeJ.

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Atp2b2^dfw/Atp2b2⁺

        C3H/HeJ-Atp2b2^dfw/J

• hearing/vestibular/ear phenotype
• abnormal cochlear microphonics (MGI Ref ID J:108888)
  • increased threshold and reduced amplitudes at high frequencies
• abnormal cochlear nerve compound action potential (MGI Ref ID J:108888)
  • increased threshold and reduced amplitudes at high frequencies
• abnormal distortion product otoacoustic emission (MGI Ref ID J:108888)
  • increased threshold and reduced amplitudes at high frequencies
• decreased brainstem auditory evoked potential (MGI Ref ID J:108888)
  • increased threshold and reduced amplitudes at high frequencies
• nervous system phenotype
• abnormal cochlear microphonics (MGI Ref ID J:108888)
  • increased threshold and reduced amplitudes at high frequencies
• abnormal cochlear nerve compound action potential (MGI Ref ID J:108888)
  • increased threshold and reduced amplitudes at high frequencies

Atp2b2^dfw/Atp2b2^dfw

        C3H/HeJ-Atp2b2^dfw/J

• hearing/vestibular/ear phenotype
• abnormal cochlear hair cell physiology (MGI Ref ID J:119503)
  • in organotypic cochlear cultures, the sensitivity of mechanoelectrical transduction channels to hair bundle displacement in outer cochlear hair cells is reduced
• abnormal hair cell mechanoelectric transduction (MGI Ref ID J:119503)
  • organotypic cultures of cochleae from P0-P3 mice (studied at P1-P4) indicate that, although the amplitude and kinetics of transduction currents in mutant OHCs from the first row of the mid-apical turn are qualitatively similar to those of wild-type controls, the curves relating bundle displacement (X) to channel opening probability, P_open (X) are shifted positively with respect to controls
  • this shift is less pronounced in Atp2b2^dfw mice (117 nm) than in Atp2b2^tm1Ges mice (175 nm)
• abnormal vestibular hair cell physiology (MGI Ref ID J:119503)
  • in organotypic utricular cultures from P0-P3 mice (studied at P1-P4), Ca²⁺ imaging of vestibular hair cells indicates that dissipation of stereociliary Ca²⁺ transients induced by Ca²⁺ uncaging is compromised
  • as a result, the Ca²⁺ clearing rate of stereocilia is decreased and therefore similar to the slower rate of cell soma
• absent brainstem auditory evoked potential (MGI Ref ID J:108888)
• absent distortion product otoacoustic emissions (MGI Ref ID J:108888)
  • responses were absent at al f2s at experimental intensity
• absent outer hair cell stereocilia (MGI Ref ID J:121326)
  • in 7 weeks old homozygous mice, stereocilia were absent from the second and third row of outer hair cells
• cochlear hair cell degeneration (MGI Ref ID J:121326)
  • in older homozygous mutants
• cochlear outer hair cell degeneration (MGI Ref ID J:121326)
  • in 7 weeks old homozygous mice, inner hair cell and their afferent terminals were present although outer hair cells appeared apoptotic
• deafness (MGI Ref ID J:14114)
  • ABR are absent indicating that they are profoundly deaf
• head bobbing (MGI Ref ID J:14114)
• behavior/neurological phenotype
• abnormal gait (MGI Ref ID J:14114)
  • walk with a hesitant and wobbly gait
• head bobbing (MGI Ref ID J:14114)
• nervous system phenotype
• abnormal cochlear ganglion morphology (MGI Ref ID J:121326)
  • in 7 weeks old homozygous mice
  • in older homozygous mutants, remaining ganglion cells contained very few cytoplasmic organelles
• cochlear ganglion degeneration (MGI Ref ID J:121326)
  • in older homozygous mutants
• abnormal cochlear hair cell physiology (MGI Ref ID J:119503)
  • in organotypic cochlear cultures, the sensitivity of mechanoelectrical transduction channels to hair bundle displacement in outer cochlear hair cells is reduced
• abnormal cochlear nucleus morphology (MGI Ref ID J:121326)
  • in anteroventral cochlear nucleus, spherical cells soma size was smaller
• abnormal hair cell mechanoelectric transduction (MGI Ref ID J:119503)
  • organotypic cultures of cochleae from P0-P3 mice (studied at P1-P4) indicate that, although the amplitude and kinetics of transduction currents in mutant OHCs from the first row of the mid-apical turn are qualitatively similar to those of wild-type controls, the curves relating bundle displacement (X) to channel opening probability, P_open (X) are shifted positively with respect to controls
  • this shift is less pronounced in Atp2b2^dfw mice (117 nm) than in Atp2b2^tm1Ges mice (175 nm)
• abnormal vestibular hair cell physiology (MGI Ref ID J:119503)
  • in organotypic utricular cultures from P0-P3 mice (studied at P1-P4), Ca²⁺ imaging of vestibular hair cells indicates that dissipation of stereociliary Ca²⁺ transients induced by Ca²⁺ uncaging is compromised
  • as a result, the Ca²⁺ clearing rate of stereocilia is decreased and therefore similar to the slower rate of cell soma
• absent outer hair cell stereocilia (MGI Ref ID J:121326)
  • in 7 weeks old homozygous mice, stereocilia were absent from the second and third row of outer hair cells
• cochlear hair cell degeneration (MGI Ref ID J:121326)
  • in older homozygous mutants
• cochlear outer hair cell degeneration (MGI Ref ID J:121326)
  • in 7 weeks old homozygous mice, inner hair cell and their afferent terminals were present although outer hair cells appeared apoptotic
• homeostasis/metabolism phenotype
• abnormal calcium ion homeostasis (MGI Ref ID J:119503)
  • in organotypic utricular cultures from P0-P3 mice (studied at P1-P4), Ca²⁺ imaging of vestibular hair cells indicates that dissipation of stereociliary Ca²⁺ transients induced by Ca²⁺ uncaging is compromised

View Research Applications

Research Applications

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

Atp2b2^dfw related

Cell Biology Research
Channel and Transporter Defects (calcium)

Neurobiology Research
Ataxia (Movement) Defects
Channel and Transporter Defects (calcium)
Vestibular and Hearing Defects

Sensorineural Research
Vestibular and Hearing Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Atp2b2dfw
Allele Name		deaf waddler
Allele Type		Spontaneous
Common Name(s)		deafwaddler; dfw;
Strain of Origin		C3H/HeJ
Gene Symbol and Name		Atp2b2, ATPase, Ca++ transporting, plasma membrane 2
Chromosome		6
Gene Common Name(s)		D6Abb2e; DNA segment, Chr 6, Abbott 2e; PMCA2; PMCA2a; PMCA2i; deaf waddler; dfw; jog; joggle; wms; wri; wriggle; wriggle mouse Sagami;
Molecular Note		A G to A transition point mutation at position 847 is predicted to cause a glycine to serine substitution at position 283 in the encoded protein. [MGI Ref ID J:48969]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

McCullough BJ; L Tempel B. 2004. Haplo-insufficiency revealed in deafwaddler mice when tested for hearing loss and ataxia. Hear Res 195(1-2):90-102. [PubMed: 15350283]  [MGI Ref ID J:92390]

Noben-Trauth K; Zheng QY; Johnson KR; Nishina PM. 1997. mdfw: a deafness susceptibility locus that interacts with deaf waddler (dfw). Genomics 44(3):266-72. [PubMed: 9325047]  [MGI Ref ID J:38429]

Street VA; McKee-Johnson JW; Fonseca RC; Tempel BL; Noben-Trauth K. 1998. Mutations in a plasma membrane Ca2+-ATPase gene cause deafness in deafwaddler mice. Nat Genet 19(4):390-4. [PubMed: 9697703]  [MGI Ref ID J:48969]

Atp2b2^dfw related

Dodson HC; Charalabapoulou M. 2001. PMCA2 mutation causes structural changes in the auditory system in deafwaddler mice. J Neurocytol 30(4):281-92. [PubMed: 11875276]  [MGI Ref ID J:121326]

Ficarella R; Di Leva F; Bortolozzi M; Ortolano S; Donaudy F; Petrillo M; Melchionda S; Lelli A; Domi T; Fedrizzi L; Lim D; Shull GE; Gasparini P; Brini M; Mammano F; Carafoli E. 2007. A functional study of plasma-membrane calcium-pump isoform 2 mutants causing digenic deafness. Proc Natl Acad Sci U S A 104(5):1516-21. [PubMed: 17234811]  [MGI Ref ID J:119503]

Konrad-Martin D; Norton SJ; Mascher KE; Tempel BL. 2001. Effects of PMCA2 mutation on DPOAE amplitudes and latencies in deafwaddler mice. Hear Res 151(1-2):205-220. [PubMed: 11124466]  [MGI Ref ID J:108888]

Lane PW. 1987. Deaf waddler (dfw) Mouse News Lett 77:129.  [MGI Ref ID J:14114]

McCullough BJ; L Tempel B. 2004. Haplo-insufficiency revealed in deafwaddler mice when tested for hearing loss and ataxia. Hear Res 195(1-2):90-102. [PubMed: 15350283]  [MGI Ref ID J:92390]

Street VA; McKee-Johnson JW; Fonseca RC; Tempel BL; Noben-Trauth K. 1998. Mutations in a plasma membrane Ca2+-ATPase gene cause deafness in deafwaddler mice. Nat Genet 19(4):390-4. [PubMed: 9697703]  [MGI Ref ID J:48969]

VanHouten JN; Neville MC; Wysolmerski JJ. 2007. The calcium-sensing receptor regulates plasma membrane calcium adenosine triphosphatase isoform 2 activity in mammary epithelial cells: a mechanism for calcium-regulated calcium transport into milk. Endocrinology 148(12):5943-54. [PubMed: 17823248]  [MGI Ref ID J:131135]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           A1

Colony Maintenance

Mating System	Homozygote x Heterozygote         (Female x Male)
	Heterozygote x Homozygote         (Female x Male)

Purchasing information

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

Pricing

Supply Details

Standard Supply	Repository-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	Usually shipped between four and eight weeks of age. This strain is included in the Mouse Mutant Resource collection. Genomic DNA is available for this strain from the Mouse DNA Resource.
Important Note	This strain may carry a chromosomal inversion on Chromosome 6 (see C3H/HeJ, Stock No. 000659).

Control Information

	Control
	Heterozygote from the colony
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

See Terms 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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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

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phone:	207-288-6470
fax:	207-288-6655

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