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 BALB/cBy-Ush1cdfcr    (Changed: 15-DEC-04 ) Type Mutant Strain; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse H2 Haplotype d

Appearance
albino, circling and head bobbing
Related Genotype: A/A Tyrp1^b/Tyrp1^b Ush1c^dfcr Tyr^c/Ush1c^dfcr Tyr^c

albino, unaffected
Related Genotype: A/A Tyrp1^b/Tyrp1^b Ush1c^dfcr Tyr^c/+ Tyr^c or A/A Tyrp1^b/Tyrp1^b + Tyr^c/+ Tyr^c

Description
Mice homozygous for either Ush1c^dfcr or Ush1c^dfcr-2J display head tossing and hyperactive circling. They are unable to orient themselves in water to swim at the surface. Despite these behavioral traits, these mice are able to breed and have normal life spans. Adult homozygotes have no auditory-evoked brainstem response. This complete deafness was found in an Ush1c^dfcr homozygote as early as 21 days of age. Scanning electron micrographs of the organ of Corti at 3 weeks of age reveal disorganized and splayed stereocilia of outer hair cells and, less severely, of inner hair cells along with degeneration of hair cells that yields a disorganized hair cell pattern. While progressive loss of hair cells and a secondary loss of spiral ganglion cells are found and are severe by 8 months of age, no gross morphological abnormalities were discerned in whole mounts of inner ears. At 9 months of age a slight peripheral retinal degeneration is found in mice homozygous for Ush1c^dfcr but not Ush1c^dfcr-2J. These phenotypes have not been identified in mice heterozygous for either allele. (Johnson et al., 2003.)

Development
The dfcr-2J allele of Ush1c arose spontaneously in the CBySmn.CB17-Prkdc^scid/J strain and was backcrossed twice to BALB/cByJ then sibling mated. In this way the Prkdc^scid mutation was removed from this strain.

Control Information

	Control
	Heterozygote from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ush1c

006853	B6.129-Ush1ctm1Xzl/Kjn
004768	B6;129S4-Ush1cdfcr-2J/J
012426	CBACa.129S6(Cg)-Ush1ctm1Bkts/J
006104	STOCK Ush1cdfcr-3J/J

View Strains carrying other alleles of Ush1c     (4 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Deafness, Autosomal Recessive 18a; DFNB18A
Usher Syndrome, Type Ic; USH1C

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Usher Syndrome, Type I; USH1   (USH1C)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Ush1c^dfcr/Ush1c^dfcr

        involves: BALB/cByJ

• behavior/neurological phenotype
• circling   (MGI Ref ID J:85400)
• head tossing   (MGI Ref ID J:85400)
• impaired balance   (MGI Ref ID J:85400)
• hearing/vestibular/ear phenotype
• abnormal inner hair cell stereociliary bundle morphology
  • at 3 weeks of age, before hair cell degeneration was apparent, examination of of the organ of Corti revealed that stereocilia of the inner hair cells displayed a milder disorganization than the outer hair cells   (MGI Ref ID J:85400)
• abnormal outer hair cell stereociliary bundle morphology
  • at 3 weeks of age, before hair cell degeneration was apparent, examination of of the organ of Corti revealed disorganization of the normally rigid and structured outer hair cell stereocilia   (MGI Ref ID J:85400)
• cochlear inner hair cell degeneration   (MGI Ref ID J:85400)
• cochlear outer hair cell degeneration   (MGI Ref ID J:85400)
• deafness
  • mice are congenitally deaf   (MGI Ref ID J:85400)
• increased or absent threshold for auditory brainstem response
  • complete absence of acoustic brainstem response at 3 weeks of age   (MGI Ref ID J:85400)
• vestibular hair cell degeneration
  • 3 month old mice displayed a progressive loss of vestibular hair cells   (MGI Ref ID J:85400)
• vision/eye phenotype
• retinal degeneration
  • a slight peripheral retinal degeneration was observed at 9 months of age   (MGI Ref ID J:85400)
• nervous system phenotype
• abnormal inner hair cell stereociliary bundle morphology
  • at 3 weeks of age, before hair cell degeneration was apparent, examination of of the organ of Corti revealed that stereocilia of the inner hair cells displayed a milder disorganization than the outer hair cells   (MGI Ref ID J:85400)
• abnormal outer hair cell stereociliary bundle morphology
  • at 3 weeks of age, before hair cell degeneration was apparent, examination of of the organ of Corti revealed disorganization of the normally rigid and structured outer hair cell stereocilia   (MGI Ref ID J:85400)
• cochlear inner hair cell degeneration   (MGI Ref ID J:85400)
• cochlear outer hair cell degeneration   (MGI Ref ID J:85400)
• vestibular hair cell degeneration
  • 3 month old mice displayed a progressive loss of vestibular hair cells   (MGI Ref ID J:85400)

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

Ush1c^dfcr/Ush1c^dfcr

        involves: BALB/cBySmn * C57BL/6 * CB17

• hearing/vestibular/ear phenotype
• abnormal cochlear hair bundle tip links morphology
  • hair bundles in the cochlea lack upper tip-link densities but do contain tip links   (MGI Ref ID J:157359)
• abnormal hair cell mechanoelectric transduction
  • resting Po and adaptation time constants are significantly reduced and slow adaptation is significantly slowed compared to wild-type   (MGI Ref ID J:157359)
  • the mean Tfast in hair cells is nearly doubled   (MGI Ref ID J:157359)
  • activation of transducer currents at similar Po was significantly slowed   (MGI Ref ID J:157359)
  • activation time constants and resting Po is reduced   (MGI Ref ID J:157359)
  • both the kinetics of channel activation and adaptation are slowed   (MGI Ref ID J:157359)
• deafness
  • by 4 weeks of age   (MGI Ref ID J:157359)
• increased or absent threshold for auditory brainstem response
  • by 4 weeks of age, auditory thresholds are greater than 90 dB   (MGI Ref ID J:157359)
• organ of Corti degeneration
  • degenerative changes in the organ of Corti are evident in mice over a few months in age   (MGI Ref ID J:157359)
• nervous system phenotype
• abnormal cochlear hair bundle tip links morphology
  • hair bundles in the cochlea lack upper tip-link densities but do contain tip links   (MGI Ref ID J:157359)
• abnormal hair cell mechanoelectric transduction
  • resting Po and adaptation time constants are significantly reduced and slow adaptation is significantly slowed compared to wild-type   (MGI Ref ID J:157359)
  • the mean Tfast in hair cells is nearly doubled   (MGI Ref ID J:157359)
  • activation of transducer currents at similar Po was significantly slowed   (MGI Ref ID J:157359)
  • activation time constants and resting Po is reduced   (MGI Ref ID J:157359)
  • both the kinetics of channel activation and adaptation are slowed   (MGI Ref ID J:157359)
• cochlear ganglion degeneration
  • degenerative changes in the organ of Corti affecting the spiral ganglion neurons are evident in mice over a few months of age   (MGI Ref ID J:157359)

View Research Applications

Research Applications

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

Ush1c^dfcr related

Neurobiology Research
Hearing Defects
Vestibular Defects

Sensorineural Research
Hearing Defects
Retinal Degeneration
Vestibular Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ush1cdfcr
Allele Name		deaf circler
Allele Type		Spontaneous
Common Name(s)		dfcr;
Strain of Origin		CBySmn.CB17-Prkdcscid/J
Gene Symbol and Name		Ush1c, Usher syndrome 1C
Chromosome		7
Gene Common Name(s)		2010016F01Rik; AIE-75; DFNB18; DFNB18A; NY-CO-37; NY-CO-38; PDZ-45; PDZ-73; PDZ-73/NY-CO-38; PDZ73; RIKEN cDNA 2010016F01 gene; harmonin; ush1cpst;
Molecular Note		The dfcr mutation is 12.7kb deletion of the 28-exon Ush1c gene. The deletion includes the last 118 nucleotides of exon 12, all of exons 13 - 15 and of alternatively spliced, inner ear-specific exons A, B, C and D, and 110 base pairs of the intron following exon D. The transcription product is spliced in all tissues examined so that exon 11 is joined, in frame, to exon 16 to produce an mRNA lacking exons 12, 13, 14 and 15 of the wild-type message, encoding 132 of the 548 amino acids comprising the ubiquitously expressed harmonin isoform a1. In the inner ear, an additional, minor splice product of the mutant transcript results from in-frame splicing of exon 11 to inner ear-specific exon E; this mRNA lacks 1137 nucleotides derived from exons 12, 13, 14, 15, A, B, C and D, encoding 379 amino acids of the wild-type inner ear-specific harmonin isoform b.Whole mount analysis revealed that the mutant protein is mislocalized to the very tips of cochlear stereocilia. [MGI Ref ID J:157359] [MGI Ref ID J:85400]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Johnson KR; Gagnon LH; Webb LS; Peters LL; Hawes NL; Chang B; Zheng QY. 2003. Mouse models of USH1C and DFNB18: phenotypic and molecular analyses of two new spontaneous mutations of the Ush1c gene. Hum Mol Genet 12(23):3075-86. [PubMed: 14519688]  [MGI Ref ID J:85400]

Additional References

Boeda B; El-Amraoui A; Bahloul A; Goodyear R; Daviet L; Blanchard S; Perfettini I; Fath KR; Shorte S; Reiners J; Houdusse A; Legrain P; Wolfrum U; Richardson G; Petit C. 2002. Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle. EMBO J 21(24):6689-99. [PubMed: 12485990]  [MGI Ref ID J:80836]

Weil D; El-Amraoui A; Masmoudi S; Mustapha M; Kikkawa Y; Laine S; Delmaghani S; Adato A; Nadifi S; Zina ZB; Hamel C; Gal A; Ayadi H; Yonekawa H; Petit C. 2003. Usher syndrome type I G (USH1G) is caused by mutations in the gene encoding SANS, a protein that associates with the USH1C protein, harmonin. Hum Mol Genet 12(5):463-71. [PubMed: 12588794]  [MGI Ref ID J:82023]

Ush1c^dfcr related

El-Amraoui A; Petit C. 2005. Usher I syndrome: unravelling the mechanisms that underlie the cohesion of the growing hair bundle in inner ear sensory cells. J Cell Sci 118(Pt 20):4593-603. [PubMed: 16219682]  [MGI Ref ID J:102194]

Gregory FD; Bryan KE; Pangrsic T; Calin-Jageman IE; Moser T; Lee A. 2011. Harmonin inhibits presynaptic Cav1.3 Ca(2) channels in mouse inner hair cells. Nat Neurosci 14(9):1109-11. [PubMed: 21822269]  [MGI Ref ID J:179787]

Grillet N; Xiong W; Reynolds A; Kazmierczak P; Sato T; Lillo C; Dumont RA; Hintermann E; Sczaniecka A; Schwander M; Williams D; Kachar B; Gillespie PG; Muller U. 2009. Harmonin mutations cause mechanotransduction defects in cochlear hair cells. Neuron 62(3):375-87. [PubMed: 19447093]  [MGI Ref ID J:157359]

Reiners J; Nagel-Wolfrum K; Jurgens K; Marker T; Wolfrum U. 2006. Molecular basis of human Usher syndrome: deciphering the meshes of the Usher protein network provides insights into the pathomechanisms of the Usher disease. Exp Eye Res 83(1):97-119. [PubMed: 16545802]  [MGI Ref ID J:116295]

Williams DS; Aleman TS; Lillo C; Lopes VS; Hughes LC; Stone EM; Jacobson SG. 2009. Harmonin in the murine retina and the retinal phenotypes of Ush1c-mutant mice and human USH1C. Invest Ophthalmol Vis Sci 50(8):3881-9. [PubMed: 19324851]  [MGI Ref ID J:154564]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• View the complete collection of spontaneous mutants in the Mouse Mutant Resource.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Heterozygote 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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