Trembler-like: A new dominant neurological mutation on Chromosome 11

Authors: Louise A. Dionne, Susan A. Cook, Patricia F. Ward-Bailey, Kenneth R.  Johnson

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: Trl

Mutation (allele) name: Trembler-like

Gene symbol: Trl

Strain of origin: C57BL/6J-Tg(RP24-226L7)28Dn

Current strain name: C3FeLe.B6-a Trl/J

Stock #: 008425 (view JAX® Mice Data Sheet for additional information including Price and Supply Information)

Phenotype categories: Neurological

Abstract

A new dominant mutation that causes affected mice to tremble has been identified and has been mapped to Chromosome 11 in the same region as trembler (Pmp22Tr-J/J) . Because Tr is a dominant allele, a direct test for allelism was inconclusive between trembler and mice carrying this new mutation.

Origin and Description

Mice carrying this new spontaneous mutation were discovered in a research colony of C57BL/6J-Tg(RP24-226L7)28Dn mice at the Jackson Laboratory. Mutant mice are recognized at about 3 weeks of age by tremors and an abnormal gait. C3FeLe.B6-a Trl/J heterozygous male mice have a high rate of being non-productive, therefore the colony is maintained by mating a heterozygous female (+/Trl) and a male C3FeLe.B6-a/J JR#198 (+/+). Backcrossing every generation has eliminated the RP24-226L7 transgene from the background strain.

Genetic Analysis

Using our standard mapping protocols C3FeLe.B6-a Trl/J mice were mated to CAST/Ei. The affected progeny from these matings were then backcrossed to a C3FeLe.B6-a/J and the progeny were used for linkage analysis. This mutation was mapped proximal to D11Mit349 (55.6 Mb) and distal to D11Mit90 (70.3 Mb).

Pathology

A pathological screen of three heterozygous mice was performed at 35, 41 and 64 weeks of age. Myelin was absent from peripheral nerves, which appeared enlarged. Peripheral hypomyelination is characteristic of previously described Pmp2 mutations.

The eyes of a heterozygous mutant at 11 months of age were examined with an ophthalmoscope and electroretinogram tests (ERG) were performed. The results were all normal.

Hearing as assessed by auditory brainstem response (ABR) testing of three heterozygous mutants at 4 weeks of age revealed that two mice had normal hearing and the third mouse had a slightly elevated threshold.

Acknowledgements

The authors wish to thank Vance Dyer for discovering the mouse, Norm Hawes for the eye examination, Chantal Long-Guess for the hearing tests and Coleen Kane for her excellent technical assistance.