Agitans-like 2 Jackson: A remutation to agitans-like on Chromosome 14.

Authors: Belinda S. Harris, Patricia F. Ward Bailey, Kenneth R. Johnson, Roderick T. Bronson, Muriel T. Davission

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

Mutation (allele) symbol: agil2J

Mutation (allele) name: agitans-like 2 Jackson

Gene symbol: agil

Strain of origin: AKR/J

Current strain name: AKR/J-agil 2J/J

Stock #: 008657 (View JAX®Mice Data Sheet for additional information including Price and Supply Information) 

Phenotype categories: neurological

Abstract

We have identified a mutation causing affected mice to have an abnormal gait that can be recognized at two weeks of age. A direct test for allelism confirmed this new mutation to be a remutation to agitans-like (agil).

Origin and Description

The agitans-like remutation was found by Bonnie Williams at The Jackson Laboratory in a production colony of AKR/J mice in 2006. Mice affected by this new mutation were initially identified by their wobbling gait. When picked up by the tail, affected mice pull in their back legs in toward their bodies. The homozygous mutant mice are smaller than their littermates, both sexes breed, and they live a normal lifespan.

Genetic Analysis

Using our standard mapping protocols, a linkage cross was set up by mating a C57BL/J female mouse to a male AKR/J mouse affected by this new mutation. No affected animals were seen in the F1 progeny produced by this cross thereby demonstrating recessive inheritance. The F1 progeny were then intercrossed and the affected homozygous F2 mice produced were utilized for linkage analysis. Use of MIT markers D14Mit133 and D14Mit101 positioned this mutation near the previously described agitans-like (agil)mutation. A direct test for allelism between two heterozygous female mice carrying the agil mutation and a male heterozygous for this new mutation produced four affected homozygotes out of thirteen progeny born, proving allelism.

Pathology

A routine pathological screen of two female homozygotes at three weeks of age showed dystrophic axons in the spinal cord and brain stem.   Two mutant males at three weeks of age had dystrophic axons and vacuoles in the spinal cord white matter, cerebellar peduncles and eighth cranial nerve root.

Hearing as assessed by auditory brainstem response testing (ABR) on three agil2J homozygotes at one month of age showed normal hearing. One control tested at the same age had normal hearing.

The eyes of these same three mice at one month of age were examined with an opthalmoscope and were determined to be normal.

Discussion

We report a remutation to agil which has pathology and a mapping postion similar to the original agil mutation. This new remutation has been named agil2J and is available from the Jackson Laboratory DNA Resource.

Acknowledgements

We thank Norman Hawes for eye examinations, Heping Yu for ABR testing, and Coleen Kane for histological preparations.