Mice homozygous for either Ush1cdfcr or Ush1cdfcr-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 Ush1cdfcr 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 Ush1cdfcr but not Ush1cdfcr-2J. These phenotypes have not been identified in mice heterozygous for either allele. (Johnson et al., 2003.)
The dfcr allele of Ush1c arose spontaneously in the CBySmn.CB17-Prkdcscid/J strain and was backcrossed twice to BALB/cByJ then sibling mated. In this way the Prkdcscid mutation was removed from this strain.
|Allele Name||deaf circler|
|Gene Symbol and Name||Ush1c, USH1 protein network component harmonin|
|Strain of Origin||CBySmn.Cg-Prkdcscid/J|
|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.|
When using the deaf circler 2 Jackson mouse strain in a publication, please cite the originating article(s) and include JAX stock #004771 in your Materials and Methods section.