A Remutation to Mbpshi named shiverer Jackson (shi-J)

Debra A. Thompson, Patricia F. Ward-Bailey, Leah Rae Donahue, Roderick T. Bronson and Muriel T. Davisson

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

Mutation (allele) symbol: shi-J

Mutation (allele) name: shiverer Jackson

Gene symbol: Mbpshi-J

Strain of origin: BALB/cJ

Current strain name: BALB/cJ-Mbpshi-J/J

Stock #: 005226 (view JAX Mice Data Sheet for additional information including Price and supply Information)

Phenotype categories: Neurological

Abstract

A neurological remutation to shiverer (a mutation in the Mbp gene) has been identified. This recessive mutation is recognized at 12 days of age, when the homozygotes show a generalized tremor during locomotion. The shivering phenotype becomes more severe with age and there is incoordination of the hindlimbs.

Origin and Description

Mice carrying the Mbpshi-J mutation were found by Laura Morse in Sept 2002 in a production colony of BALB/cJ mice at the Jackson Laboratory and were brought to the Mouse Mutant Research (MMR) deviant search program. Homozygous mutants are easily recognized at 12 days of age by their generalized tremor during locomotion. Weaning must be delayed Mbpshi-J homozygotes until they reach at least 5 weeks of age. This strain is maintained by cross-intercross in which obligate heterozygotes are intercrossed and homozygous offspring are bred to their +/? siblings to again generate obligate heterozygotes.

Genetic Analysis

Based on the phenotypic similarity of this new mutation to the previously described mutant shiverer (Mbpshi), a direct test for allelism was performed by mating a male  BALB/Cha.SWV(c3Fe)-Mbpshi/J mouse to a female  BALB/cJ-Mbpshi-J/J. This mating produced 10 progeny of which 4 had the shiverer phenotype proving allelism.

Pathology

A routine pathological screen  was done with 6 mice (1 homozygous shi-J/shi-J mutant and 1 littermate (+/?) control pair, each at 7, 9, and 10 weeks of age). For purposes of comparison a pathological screen was also done on two homozygous shi/shi mutants and a littermate control. The BALB/cJ-Mbpshi-J/J mutants lacked CNS myelin, like the original shiverer and the controls had normal myelin.

Hearing was assessed by auditory brainstem response (ABR) testing on 2 mutants and 3 (+/?) controls. The 2.5 month-old mutants had 10 - 20 dB elevated thresholds  and abnormal wave patterns with long interpeak latencies characteristic of a myelin defect. The 3 controls had normal threshold and normal interpeak latency.

An electroretinogram (ERG) test was done on 2 mutants and 3 (+/?) controls and was normal.

Acknowledgements

The authors wish to thank Laura Morse for the discovery of the mutant and Heping Yu for the ABR testing, Norm Hawes for the Electroretinogram (ERG) and Coleen Marden for pathological expertise.