Description

Strain Information

Type Coisogenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation [N1p]F1N2F9 (06-DEC-07)

Appearance
black, circling
Related Genotype: a/a Pcdh15^av-3J/Pcdh15^av-3J

black, unaffected
Related Genotype: a/a Pcdh15^av-3J/+

Description
There have been several remutations to Ames waltzer (av) have occurred in stocks at The Jackson Laboratory. All mice homozygous for these remutations show the characteristic head-tossing, circling, and deafness characteristic of Ames waltzer. Ames wa ltzer 2J homozygous mutant mice (av^2J/av^2J) are more severely afflicted than mice homozygous for the other Jackson (J) remutations. av^2J/av^2J homozygotes become disoriented and sink in swim tests; Ames waltzer 3J homozygotes (av^3J/av^3J), like Ames waltzer-J (av^J/av^J), swim with difficulty and circle afloat. In the membranous labyrinth the fluid spaces in the Organ of Corti fail to develop. Later, hair cells and spiral ganglion cells degenerate.

Development
Ames waltzer 3 Jackson (Pcdh15^av-3J) arose spontaneously on strain C57BL/6J when it was at F175 at the Jackson Laboratory in the early 1990's. It was maintained on that strain and was cryopreserved in 1993 by mating homozygous males at F175+1N2F1 to C57BL/6J females.

Control Information

	Control
	Heterozygote from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Pcdh15

000517	B6.BKS-Pcdh15av-J/J
002078	B6C3Fe a/a-Pcdh15av-2J/J
004156	C57BL/6J-Pcdh15av-5J/J

View Strains carrying other alleles of Pcdh15     (3 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Pcdh15^av-3J/Pcdh15^av-3J

        C57BL/6J-Pcdh15^av-3J/J

• hearing/vestibular/ear phenotype
• *normal* hearing/vestibular/ear phenotype (MGI Ref ID J:106625)
  • normal endocochlear potential
  • histochemistry of the organ of Corti shows the centrosomes in the normal position
  • cytocauds are not observed
• abnormal cochlear hair cell morphology (MGI Ref ID J:106625)
  • diminished amounts of actin in the stereocilia and cuticular plate
• abnormal cochlear hair cell inter-stereocilial links (MGI Ref ID J:135991)
  • lateral links that connect stereocilia to each other are sparse and frequently disrupted
• abnormal cochlear hair bundle tip links (MGI Ref ID J:135991)
  • apical links are not present in P5 mice
• abnormal cochlear outer hair cell morphology (MGI Ref ID J:106625)
• abnormal outer hair cell stereociliary bundle morphology (MGI Ref ID J:106625)
  • E18.5 embryos have disorganized and fragmented outer hair cell (OHC) stereociliary bundles
  • stereociliary generally assemble into two to three clumps at the cell apical surface instead of forming single V-shaped bundles
  • kinocilia are often dissassocaited from the stereociliary clumps
• abnormal inner hair cell stereociliary bundle morphology (MGI Ref ID J:106625)
  • E17.5 embryos have disorganized and fragmented inner hair cell (IHC) stereociliary bundles
  • stereociliary generally assemble into two to three clumps at the cell apical surface instead of forming single V-shaped bundles
  • kinocilia are often dissassocaited from the stereociliary clumps
• abnormal orientation of cochlear hair cell stereociliary bundles (MGI Ref ID J:135991)
  • kinocillia show large mean deviations from the plane cell polarity axis (PCP) with only 26% of the kinocillia being within 15 degrees of the PCP compared to 84% in wild-type mice
  • the mean absolute kinociliary deviation is 38 degrees compared to 8 degrees in wild-type mice
• short cochlear hair cell stereocilia (MGI Ref ID J:106625)
• absent brainstem auditory evoked potential (MGI Ref ID J:106625)
  • as early as 9 days of age there is no ABR response even at 20 kHz
• absent linear vestibular evoked potential (MGI Ref ID J:116914)
  • VESPs are absent at the maximum stimulus intensity used
• circling (MGI Ref ID J:106625)
• behavior/neurological phenotype
• abnormal reflex (MGI Ref ID J:116914)
  • abnormal drop reflex; mice do not demonstrate expected dorsoflexion and spread out the front paws when quickly lowered from ~20 cm above a table surface, while controls do exhibit this behavior
• circling (MGI Ref ID J:106625)
• impaired swimming (MGI Ref ID J:106625)
  • 3 of 4 mice tested exhibit poor swimming ability; mice can not maneuver in the water and can not remain at the surface
• nervous system phenotype
• abnormal cochlear hair cell morphology (MGI Ref ID J:106625)
  • diminished amounts of actin in the stereocilia and cuticular plate
• abnormal cochlear hair cell inter-stereocilial links (MGI Ref ID J:135991)
  • lateral links that connect stereocilia to each other are sparse and frequently disrupted
• abnormal cochlear hair bundle tip links (MGI Ref ID J:135991)
  • apical links are not present in P5 mice
• abnormal cochlear outer hair cell morphology (MGI Ref ID J:106625)
• abnormal outer hair cell stereociliary bundle morphology (MGI Ref ID J:106625)
  • E18.5 embryos have disorganized and fragmented outer hair cell (OHC) stereociliary bundles
  • stereociliary generally assemble into two to three clumps at the cell apical surface instead of forming single V-shaped bundles
  • kinocilia are often dissassocaited from the stereociliary clumps
• abnormal inner hair cell stereociliary bundle morphology (MGI Ref ID J:106625)
  • E17.5 embryos have disorganized and fragmented inner hair cell (IHC) stereociliary bundles
  • stereociliary generally assemble into two to three clumps at the cell apical surface instead of forming single V-shaped bundles
  • kinocilia are often dissassocaited from the stereociliary clumps
• abnormal orientation of cochlear hair cell stereociliary bundles (MGI Ref ID J:135991)
  • kinocillia show large mean deviations from the plane cell polarity axis (PCP) with only 26% of the kinocillia being within 15 degrees of the PCP compared to 84% in wild-type mice
  • the mean absolute kinociliary deviation is 38 degrees compared to 8 degrees in wild-type mice
• short cochlear hair cell stereocilia (MGI Ref ID J:106625)

View Research Applications

Research Applications

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

Pcdh15^av-3J related

Neurobiology Research
Vestibular and Hearing Defects

Sensorineural Research
Vestibular and Hearing Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Pcdh15av-3J
Allele Name		Ames waltzer 3 Jackson
Allele Type		Spontaneous
Common Name(s)		av3J;
Strain of Origin		C57BL/6J
Gene Symbol and Name		Pcdh15, protocadherin 15
Chromosome		10
Gene Common Name(s)		Ames Waltzer; BB078305; DFNB23; DKFZp667A1711; USH1F; av; expressed sequence BB078305; neuroscience mutagenesis center, 19; neuroscience mutagenesis facility, 19; nmf19;
General Note		These homozygotes, like Pcdh15av-J homozygotes, can swim, though with difficulty. They tend to circle while afloat (J:28688).
Molecular Note		An insertion of a single A nucleotide after position 4521 in the coding region results in a frameshift and a premature stop codon. Any encoded protein is predicted to lack a cytoplasmic domain. [MGI Ref ID J:66738]

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

Alagramam KN; Murcia CL; Kwon HY; Pawlowski KS; Wright CG; Woychik RP. 2001. The mouse ames waltzer hearing-loss mutant is caused by mutation of pcdh15, a novel protocadherin gene Nat Genet 27(1):99-102. [PubMed: 11138007]  [MGI Ref ID J:66738]

Hampton LL; Wright CG; Alagramam KN; Battey JF; Noben-Trauth K. 2003. A new spontaneous mutation in the mouse Ames waltzer gene, Pcdh15. Hear Res 180(1-2):67-75. [PubMed: 12782354]  [MGI Ref ID J:84779]

Osako S; Hilding DA. 1971. Electron microscopic studies of capillary permeability in normal and ames waltzer deaf mice. Acta Otolaryngol (Stockh) 71(5):365-76. [PubMed: 5093631]  [MGI Ref ID J:5225]

Pcdh15^av-3J related

Alagramam KN; Murcia CL; Kwon HY; Pawlowski KS; Wright CG; Woychik RP. 2001. The mouse ames waltzer hearing-loss mutant is caused by mutation of pcdh15, a novel protocadherin gene Nat Genet 27(1):99-102. [PubMed: 11138007]  [MGI Ref ID J:66738]

Ball SL; Bardenstein D; Alagramam KN. 2003. Assessment of retinal structure and function in Ames waltzer mice. Invest Ophthalmol Vis Sci 44(9):3986-92. [PubMed: 12939319]  [MGI Ref ID J:85211]

Cook S; Lane P. 1993. Re-mutation to Ames waltzer Mouse Genome 91:554.  [MGI Ref ID J:28688]

Jones SM; Johnson KR; Yu H; Erway LC; Alagramam KN; Pollak N; Jones TA. 2005. A quantitative survey of gravity receptor function in mutant mouse strains. J Assoc Res Otolaryngol 6(4):297-310. [PubMed: 16235133]  [MGI Ref ID J:116914]

Lefevre G; Michel V; Weil D; Lepelletier L; Bizard E; Wolfrum U; Hardelin JP; Petit C. 2008. A core cochlear phenotype in USH1 mouse mutants implicates fibrous links of the hair bundle in its cohesion, orientation and differential growth. Development 135(8):1427-37. [PubMed: 18339676]  [MGI Ref ID J:135991]

Raphael Y; Kobayashi KN; Dootz GA; Beyer LA; Dolan DF; Burmeister M. 2001. Severe vestibular and auditory impairment in three alleles of Ames waltzer (av) mice. Hear Res 151(1-2):237-249. [PubMed: 11124469]  [MGI Ref ID J:106625]

Senften M; Schwander M; Kazmierczak P; Lillo C; Shin JB; Hasson T; Geleoc GS; Gillespie PG; Williams D; Holt JR; Muller U. 2006. Physical and functional interaction between protocadherin 15 and myosin VIIa in mechanosensory hair cells. J Neurosci 26(7):2060-71. [PubMed: 16481439]  [MGI Ref ID J:105750]

Zheng QY; Yan D; Ouyang XM; Du LL; Yu H; Chang B; Johnson KR; Liu XZ. 2005. Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans. Hum Mol Genet 14(1):103-11. [PubMed: 15537665]  [MGI Ref ID J:95655]

Zheng QY; Yu H; Washington JL rd; Kisley LB; Kikkawa YS; Pawlowski KS; Wright CG; Alagramam KN. 2006. A new spontaneous mutation in the mouse protocadherin 15 gene. Hear Res 219(1-2):110-20. [PubMed: 16887306]  [MGI Ref ID J:111661]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           A1

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.

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

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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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