Tremor and reduced lifespan 2 Jackson: a new remutation on Chromosome 10.

Authors: Son Yong Karst, Patricia F. Ward-Bailey, Richard Samples, Kenneth R. Johnson, Leah Rae Donahue and Muriel T. Davisson

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: trls2J

Mutation (allele) name: tremor and reduced lifespan 2 Jackson

Gene symbol: trls2J

Strain of origin: WB/ReJ-KitW/J

Current strain name: B6.WB-trls2J/J

Stock #: 008723  (view JAX® Mice Data Sheet for additional information including Price and Supply Information)

Phenotype categories: neurological

Abstract 

A new neurological mutation has been identified and characterized as a remutation of tremor and reduced lifespan (trls), as shown by a direct test for allelism. The new mutation was named tremor and reduced lifespan 2 Jackson (trls2J).

Origin and Description

This new spontaneous mutation arose in a breeding colony of WB/ReJ-KitW/J mice at the Jackson Laboratory and was discovered by Jessica Rau.

Mice homozygous for the trls2J mutation can be recognized at about 14 days of age by a moderate tremor and smaller body size than their littermates. Progressive weakness and wasting follows,  and death occurs by 3-4 weeks of age, but mutants seldom live longer than 4 weeks. The description of the original trls mice states that mutant mice are rarely able to survive to 10 weeks of age.

The trls2J colony is maintained by breeding hosts of homozygous ovarian transplants to C57BL/6J mice and than intercrossing the heterozygous offspring.

These matings were continued for four backcross generations to C57BL/6J  without seeing any mice with the KitW(diluted black with white belly spot) phenotype.

Heterozygous (trls2J/+) mice can live normal life spans and are good breeders.

Genetic Analysis

A mouse homozygous for the trls2J mutation was mated to a CAST/EiJ mouse. The F1 mice from this mating produced a normal looking phenotype, proving that this mutation has recessive inheritance.

Based on phenotypic similarities, a direct test for allelism was performed by mating WB/ReJ-KitW/J mice carrying this new mutation to BKS(Cg)-trls/J mice (+/trls). Three mating pairs were set up that produced 40 progeny, of which 13 pups had the trls mutant phenotype, proving allelism.

The original trls mutation was mapped to Chromosome 10 between D10Mit115 (NCBIm 34 position 70.3 Mb) and D10Mit65 (NCBIm 34 position 84.1 Mb) and is non-recombinant with D10Mit7 (NCBIm 34 position 81.2Mb) and D10Mit42 (NCBIm 34 position 82.5 Mb).

Pathology

A routine pathological examination of one homozygous mouse at 5 weeks of age showed testicular atrophy and two homozygous mice at 3 weeks of age had atrophic thymuses.

The eyes of one mutant mouse at age 4 weeks were tested by electroretinogram (ERG) and found to be normal.

Hearing as assessed by auditory brainstem response testing (ABR) of two mutant mice at 4 weeks of age and one mutant mouse at 3 weeks of age showed normal thresholds, but there were noticable peaks with long latencies, which may indicate deficient myelin.

Acknowledgements

We thank Jessica J. Rau for discovery of the mutant, Roderick Bronson and Coleen Kane for pathological screening, Heping Yu and Chantal Longo-Guess for hearing assessment, Norm Hawes and Ron Hurd for eye examinations.