Jackson shaker 2 Jackson, a new spontaneous mouse mutation in the Ush1g gene.
Leona Gagnon, Leah Davis* and Kenneth R Johnson
Source of Support: This research was supported by NIH/NCRR grant RR01183 to the Mouse Mutant Resource (M.T. Davisson, PI) and NIH/NIDCD grant DC04301 (K.R. Johnson, PI).
*Summer Student internship program supported by the National Science Foundation, the Barbara H. Sanford Endowed Scholarship Fund, and the Horace W. Goldsmith
Mutation (allele) symbol: js-2J
Mutation (allele) name: Jackson shaker 2 Jackson
Gene symbol: Ush1g
Strain of origin: B6.Cg-T2J+/+qk
Current strain name: B6(Cg)-Ush1gjs-2J/J
Stock #: 006111
Phenotype categories: neurological/behavioral: motor capabilities/coordination/movement anomalies/deafness/head bobbing
Origin and Description
The recessively inherited spontaneous mouse mutation Jackson shaker 2 Jackson (js-2J) was identified in 2002 in a research colony (B6.Cg-T2J+/+qk) of Eva Eicher's. Mutant mice display head tossing and circling behavior indicative of vestibular dysfunction and hearing loss. Mutant mice were crossed to C57BL/6J and intercrossed. Mice that displayed the new circling behavior but not the T or qk phenotypes were selected for breeding, thus producing the current colony designated B6(Cg)-Ush1gjs-2J/J. The colony is now maintained by brother/sister mating of a heterozygous female and a circling mutant male.
A routine pathological screen revealed no gross abnormalities in mutant mice as compared with a control littermate with the exception of hair cell loss observed in the inner ear. Four mutant mice and two littermate controls were assessed for hearing by auditory brainstem response (ABR). All mutants (12-54 days old) were deaf (no response at the highest stimulus presented, 100dB) while their control littermates retained good hearing (normal ABR threshold). A clinical eye exam revealed no abnormalities.
Genetic Analysis
An intercross was performed with CAST/Ei and 54 F2 animals were analyzed. Using our standard mapping practice, the mutation was mapped to a region of chromosome 11 where the Ush1g gene is located.
A complementation test was performed between mice heterozygous for the new mutation in the Ush1g gene and Jackson shaker (js), a mouse mutation previously identified in the Ush1g gene. The test-cross produced two litters with a total of 14 mice, five of which were mutant, thus confirming allelism.
To characterize the newmutation at the DNA level, PCR primers were designed to amplify each exon of the Ush1g gene including the splice donor and acceptor recognition sequences. Each PCR product was sequenced at The Jackson Laboratory core sequencing facility. Each exon's sequence was then compared to the mouse sequence publicly available, and a 155 base pair deletion was detected within exon 2 of the Ush1g gene (Fig1.) The deletion induces a frame-shift coding for 51 altered amino acids and then a premature stop codon (Fig2.)
Acknowledgements
We thank Linda Washburn for identification of the original Jackson shaker 2 Jackson mutant mouse, Sandra Gray for mouse colony development, Heping Yu and Chantal Longo-Guess for ABR analysis, Coleen Marden and Rod Bronson for pathological screening and Norm Hawes for clinical eye evaluation.
