A new spontaneous mutation in the Ush1c gene named deaf circler 3 Jackson
Authors: Kelly L. Kane, Leona Gagnon and Kenneth R. Johnson
Source of Support: This research was supported by NIDCD/NIH grant DC04301 (K R Johnson) and NCRR/NIH grant RR01183 (M T Davisson)
Mutation (allele) symbol: dfcr-3J
Mutation (allele) name: Deaf circler 3 Jackson
Gene symbol: Ush1c
Strain of origin: STOCK Tg(CAG-Bgeo/GFP)21Lbe/J
Current strain name: STOCK Ush1cdfcr-3J/J
Stock #: 006104 (view JAX® Mice Data Sheet for additional information including Price and Supply Information)
Phenotype categories: neurological/behavioral: motor capabilities/coordination/movement anomalies/deafness/circling
Origin and Description:
The recessively inherited, spontaneous mutation named deaf circler 3 Jackson (dfcr-3J) was originally discovered by Lori Knowles in the Stock Tg(ACTB-Bgeo/GFP)21 Lbe colony of mice (Stock # 003920). Mutant mice display head bobbing and rapid circling behaviors, which are commonly indicative of vestibular dysfunction and often accompanied by hearing loss. The mutant mice were crossed to C57BL/6J mice, and the Tg mutation was deleted from the colony by selective mating (confirmed by genotyping), creating the new strain designated STOCK Ush1cdfcr-3J /J. The colony is currently maintained by brother/sister mating of a homozygous male and heterozygous female.
Genetic Analysis:
An intercross was performed with CAST/EiJ mice, and 60 mutant F2 animals were analyzed. Using our standard mapping practice, the mutation was mapped to the region on Chromosome 7 where the Ush1c gene is located. Due to the mapped proximity of the Ush1c gene, a complementation test for allelism was performed between mice heterozygous for the new mutation and mice heterozygous for the deaf circler (dfcr) mutation of the Ush1c gene, also known to cause circling behavior and deafness. The test-cross produced 3 litters with a total of 30 mice, 4 of which had mutant phenotypes, thus confirming allelism.
Pathology:
A routine pathological screen of a 46-week-old mutant female mouse and a heterozygous male littermate revealed no gross structural abnormalities in the mutant except for dilated renal tubules that are likely due to the advanced age of the animal. Examination of whole mounts of inner ears isolated from 2 mutant females and one littermate control showed no gross structural abnormalities or abnormalities of the otoconia in the utricle or saccule. A detailed examination of inner ears for hair cell abnormalities was not undertaken.
The auditory brainstem response (ABR) was used to assess the hearing of two mutant mice and a littermate control at 6 weeks of age. The mutant mice were deaf showing no response at the highest stimulus presented (100 dB SPL), while the littermate controls exhibited good hearing. A clinical eye exam revealed no abnormalities.
Acknowledgements:
We thank the Lori Knowles for the discovery of the original deaf circler 3 Jackson mutant mouse, Sandra Gray for mouse colony development, Heping Yu for ABR analysis, Coleen Marden and Rod Bronson for pathological screening, and Norm Hawes for clinical eye evaluation.
