Snell's waltzer 4 Jackson, a new spontaneous mutation in the Myo6 gene

 

Kelly Kane, 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: Myo6 sv-4J

Mutation (allele) name: Snell's waltzer 4 Jackson

Gene symbol: Myo6

Strain of origin: 129S1/SvImJ

Current strain name: 129S1/SvImJ-Myo6sv-4J/J

Stock #:008456 (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 mouse mutation Snell's waltzer 4 Jackson (sv-4J) was identified by Rachel Miller in 2004 in an inbred 129S1/SvImJ colony. Mutant mice display head tossing and circling behavior commonly indicative of vestibular dysfunction and probable hearing loss. The hearing of 3 mutant mice and 5 heterozygous littermate controls was assessed by measuring their auditory brain stem response (ABR) thresholds at 6-7 weeks of age. All mutant mice were deaf showing no response to the highest stimulus presented (100 dB SPL), 2 of the heterozygous littermates had moderate hearing loss (~15 dB threshold elevations) while the other 3 exhibited good hearing (indicated by normal ABR thresholds). A routine pathological screen of a mutant female mouse and a heterozygous male littermate revealed no gross structural abnormalities in the mutant. Examination of whole mounts of inner ears isolated from 2 mutant males and one littermate control also showed no gross structural abnormalities or abnormalities of the otoconia in the utricle or saccule.

Genetic Analysis

 

An intercross was performed with CAST/EiJ mice and 70 mutant F2 animals were analyzed. Using our standard mapping practice the mutation was mapped to a region of Chromosome 9 between markers D9Mit177 (78 Mb position, NCBI Build 36) and D9Mit196 (86 Mb). The myosin 6 gene (Myo6) is located within this region (80 Mb) and was identified as a good candidate gene because mutations in this gene, including the original Snell's waltzer mutation) have been previously shown to cause head tossing, circling behavior and hearing loss. A complementation test was set up between a female heterozygous for the new mutation and a male homozygous for the Myo6sv-2J mutation. The mating produced 2 litters with a total of 13 animals of which 6 were mutant, thus confirming allelism.

  

Acknowledgements

We thank Rachel Miller for the identification of the original Snell's waltzer 4 Jackson mutant mouse, Sandra Gray for mouse colony management, Leona Gagnon for mapping assistance, Heping Yu for ABR analysis, and Coleen Marden and Rod Bronson for pathological screening.