awag:A New Mouse Mutation with a Late Onset Abnormal Gait Maps to Mouse Chromosome 2

Belinda Harris, Patricia Ward Bailey, Kenneth Johnson, Rod Bronson, and Muriel Davisson.

Source of Support: This research was supported by grants RR01183 to the Mouse Mutant Resource (M.T. Davisson, PI) and Cancer Core Grant CA34196.

Mutation (allele) symbol: awag

Mutation (allele) name: Ages With Abnormal Gait

Gene symbol: awag

Strain of origin: C57BL/6J-Tyrc-2J/J

Current strain name: C57BL/6J-Tyrc-2J-awag/J

Stock #:005349  (View JAX®Mice Data Sheet for additional information including Price and Supply Information) 

Phenotype categories: neuromuscular

Abstract

A new spontaneous mouse mutation named "ages with abnormal gait" (awag) has been identified. The mutant mice look like normal control littermates until they are about 2 months of age when a distinct tremor is observed when they walk. This mutation was mapped using an intercross with CAST/Ei and was found to be on Chromosome 2.

Origin and Description

A new spontaneous mouse mutation named "ages with abnormal gait " was discovered in 1998 by Jay Wellington in a production colony of C57BL/6J-Tyrc-2J/J mice at The Jackson Laboratory. Mutants have a distinct tremor when walking that first appears around 2 months of age. When lifted by the tail the mutant mice do not splay their hind legs out as normal mice do, instead they hold their legs in a bowlegged umbrella like way and arch their backs. Mutant mice of both sexes breed and live a normal life span. The mutant strain is maintained by mating heterozygous siblings or by mating female homozygotes with untested male littermate controls.

Genetic Analysis

Using our standard mapping procedures  an intercross between the strains C57BL/6J-Tyrc-2J-awag/J and CAST/Ei was set up and generated 30 affected F2 progeny of which 21 were used  for linkage analysis. The mutation maps between D2Mit7 at Ensembl psition 38.1 mb (1/36 recombinants) and D2Mit72 at Ensembl position 49.2 Mb (2/36 recombinants) and is non-recombinant with D2Mit320 at Ensembl psition 39.1, D2Mit237 at Ensembl position 40.9 mb, and D2Mit322 at Ensembl position42.8. To prevent errors of misclassification, only  mice with the most obvious mutant phenotype were included in the linkage analysis.

Pathology

Hearing as assessed by ABR  in mutant animals showed variable results. Two mutants at 3 months of age had hearing loss. Two other awag mutants tested at 6 months had normal to almost normal hearing. All controls had normal hearing. The eyes of both mutant and control mice were examined with an opthalmascope and all animals tested had corneal holes and cataracts.These observations of the eyes are characteristic of the background strain and not the result of this new mutation. Comprehensive histopathologic examination (Our Standard Pathology screen) of 7 mutant mice ranging in age from 3-18 months showed no significant lesions in somatic organs. Three had mild hydrocephalus, assumed to be a strain background occurence.

Discussion

We report on a new spontaneous mouse mutation on Chromosome 2 that causes an abnormal gait in homozygotes. This new mutant differs from many of the neuromuscular mutants such as tottering, staggerer, waddles, wobbler, abnormal wobbly gait, shiverer, etc. ( MGI),  in that the awag phenotype is not observed until mutants are about 2 months of age, and also awag mutants live a normal life span.

Acknowledgements

The authors would like to thank Norm Hawes for examination of the eyes, Heping Yu for hearing assessment, and Coleen Marden, for expert technical expertise.

References

MGD 2004, Mouse Genome Database, Mouse Genome Informatics Project, The Jackson Laboratory, Bar Harbor, ME. (URL: http://www.informatics.jax.org).

Ensembl, Mouse Genome Assembly NCBI m33