A Neurological Mutation on Chromosome 14 named shimmy 2 Jackson.

Patricia Ward-Bailey, Richard Samples, Jieping Wang, Leah Rae Donahue, Roderick 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: shmy2J

Mutation (allele) name: shimmy 2 Jackson

Gene symbol: shmy

Strain of origin: B10.D1-H2q/SgJ/J

Current strain name: B10.D1-H2q/SgJ-Shmy2J/J

Stock #: 005133 (view JAX® Mice Data Sheet for additional information including Price and Supply Information). NOTE: As of 1-4-07 available as DNA only from the Jackson Laboratory DNA Resource.

Phenotype categories: neurological

Abstract

A neurological mutation exhibiting a shaky/wobbly gait has been identified and mapped to Chromosome 14 in the same region as the mutation shimmy (shmy).  A complementation test for allelism between this new mutant  and the shimmy mice produced affected animals proving that they are allelic.

Origin and Description

Mice carrying the spontaneous recessive shmy2J mutation were found by Marianne Urquhart in October 2001, in a production colony of B10.D1-H2q/SgJ/J mice at The Jackson Laboratory and were brought to The Mouse Mutant Resource (MMR). Homozygous mutants are easily recognized by 5 weeks of age by their shaking and wobbly gait. The mice appear to vibrate and this vibration can be felt when the mice are held by their tails.

Genetic Analysis

Using our standard mapping protocols  an intercross between B10.D1-H2q/SgJ-shmy2J/J  and CAST/Ei F1 hybrids was set up and generated 42 affected  F2 animals for linkage analysis. The shmy2J mutation maps to mouse Chromosome 14,  distal to D14Mit252 (at 6.0 cM) and proximal to D14Mit45 (at 12.5cM). The previously described mutation shimmy (shmy) has been mapped to position 6.5 cM.  A direct test for allelism was set up by mating a mouse homozygous for this new mutation with a mouse homozygous for the  original shmy mutation. From this mating 4 progeny out of 7 born were affected proving that  the new mutation is an allele of shimmy.

Pathology

A pathological screen  of one  shmy2J/shmy2J mutant and one control littermate at 3 months of age revealed no gross lesions. Similarly, the pathological studies of the original shmy showed a very few dystrophic axons in the lateral nucleus of the cerebellum in mutants, but did not reveal the cause of the neurological phenotype (Lane, et al.1994).

Hearing of four homozygotes and two heterozygotes as assessed by ABR testing was determined to be normal.

Discussion

The similarity in neurological phenotype, chromosomal location, and the results of the test for allelism confirm that shmy2Jis a remutation to shimmy (shmy).  Likewise, the chromosomal location and  similarity of the locomoter phenotypes of shmy snd shmy2J, with the BK Channel  (BK-/- ) knockout mice (Sausbier, et al.2004), make the  Kcnma1 gene a good candidate for the shmy mutation.

Acknowledgements

The authors wish to thank Marianne Urquhart for discovery of the mutant mice, Coleen Marden for excellent technical skills, and Heping Yu for ABR testing.

References

Lane PW, Cook SA, Bronson RT, Johnson  KR, and Davisson MT. Shimmy (shmy), A New Mutation On Chromosome 14 Of The Mouse. Mouse Genome 1994, 92(4), 686-687.

Mouse Genome Database (MGD) Mouse Genome Informatics Project, The Jackson Laboratory, Bar Harbor, Maine. World Wide Web

(URL http://www.informatics.jax.org)

Sausbier M, Hu H, Arntz C, Feil S, Kamm S, Adelsberger H, Sausbier U, Sailer CA, Feil R, Hofmann F, Korth M, Shipton MJ, Knaus HG, Wolfer DP, Pedroarena CM, Storm JF, Ruth P. Cerebellar ataxia and Purkinjie cell dysfunction caused by Ca2+-activated K+ channel deficiency. Proc Natl Acad Sci USA 2004, 101(25), 9474-8.