Myotonia 9 Jackson; a new remutation in the Clcn1 gene.

Belinda Harris, Patricia Ward Bailey, Kenneth Johnson, and Roderick Bronson

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

Mutation (allele) symbol: Clcn1adr-mto9J

Mutation (allele) name: myotonia 9 Jackson

Gene symbol: Clcn1

Strain of origin: C57BL/6J

Current strain name: C57BL/6J-Clcn1adr-mto-9J

Stock #: 008253 (view JAX® Mice Data Sheet for additional information including Price and Supply Information)

Phenotype categories: neurological

Abstract

We have identified a new remutation of the Clcn1 gene by a direct test of allelism. The stiffened rear leg phenotype of the new Clcn1adr-mto9J  remutation is very similar to that caused by the original Clcn1adr-mto mutation, however may be less severe in this new remutation.

Origin and Description

The Clcn1adr-mto9J  remutation was found in 2005 by Stacey L. Dannenberg in a colony of  ENU treated C57BL/6J mice at The Jackson Laboratory and was first recognized by the rear leg paralysis. Mice homozygous for this new remutation stiffen their rear legs when touched and this stiffening can be recognized by two weeks of age. Affected mice are smaller in size and thinner than littermate controls (See Photo) and exhibit hind end hair loss.

Genetic Analysis

This new mutant was shown to be an allele of myotonia (Clcn1adr-mto) by mating a heterozygous female BALB/cByJ- Clcn1adr-mto2J mouse to a male mouse heterozygous for this new mutation. This mating produced 2 affected mice out of 25 born, proving allelism.

Pathology

Routine pathological screening showed that one homozygous male at 13 weeks, and one homozygous female and one male at seven weeks of age had no lesions.

The eyes of three homozygous Clcn1adr-mto9J mutant mice and two littermate controls at 1 month of age were examined with an opthalamascope and were determined to be normal. Electroretinogram (ERG) testing was also normal.

Hearing as assessed by auditory brainstem response (ABR) testing of three homozygous Clcn1adr-mto9J mutant mice and two littermate controls at 1 month of age showed normal hearing in all mice.

Discussion

This new remutation has been shown to have a very similar, but milder phenotype compared to that of the original myotonia mutants. Clcn1adr-mto9J will be available from The Jackson Laboratory DNA Resource. No embryos will be cryopreserved.

Acknowledgements

The authors would like to thank Norm Hawes for eye examinations, Heping Yu for ABR testing, and Coleen Marden for excellent pathological skills.