Tiny wasting (tnyw); a new autosomal recessive mutation on Chromosome 3

Coleen Marden, Patricia F. Ward-Bailey, Leah Rae Donahue, Roderick T. Bronson, and Kenneth R. Johnson

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

Mutation (allele) symbol: tnyw

Mutation (allele) name: tiny wasting

Gene symbol:

Strain of origin: B6,129-Pemt2^tmlJ

Current strain name: B6,129-Pemt2^tmlJ- tnyw/J

Stock #: 005323 (view JAX® Mice Data Sheet for additional information including Price and Supply Information)

Phenotype categories: size, neurological

Abstract

A new autosomal recessive mutation has been identified and named tiny wasting (tnyw). This mutation in the homozygous state causes affected mice to exhibit runting, an inability to coordinate movement, and premature death at around 3 weeks of age. This new mutation has been mapped to Chromosome 3.

Origin and Description

The tnyw mutation arose in a research colony of B6,129-Pemt2^tmlJ mice at the Jackson Laboratory and was discovered by Leah Rae Donahue. This mutation causes a variable phenotype. All homozygotes have a reduced lifespan with most animals dying by 3 weeks of age (See photo-3 weeks of age). All mutants are smaller in size compared to their unaffected littermates. Some mutants are unable to right themselves or have abnormal locomotion. Homozygotes can be identified by two weeks of age by their smaller wasting bodies. (See Photo-2 weeks of age) The tnyw colony is maintained by transplanting the ovaries of an affected female into a C3Smn.CB17-Prkdc^scid/J female mouse that is then mated to a tnyw heterozygote male mouse.

Genetic Analysis

In order to find the chromosomal location of the tnyw mutation a linkage cross was set up by mating an ovarian transplanted female mouse homozygous for the tynw mutation to a CAST/Ei male. The tested heterozygous F1 progeny from this cross were then intercrossed and in 7 matings produced 80 F2 mutant mice. The tynw mutation is inherited recessively as shown by traditional linkage cross analysis. No mutants were seen in the F1 generation of the linkage cross, and 25% of the F2 progeny produced were mutants, as expected.

Using our standard mapping protocols we mapped this new mutation to Chromosome 3. Linkage was first found with microsatellite markers D3Mit11 (NCBI 36 position 100.6 Mb) and D3Mit29 (NCBI 36 position 90.7 Mb), both showing 2.4 % recombination. The mutation maps between D3Mit11 and D3Mit288 (NCBI 36 position 121.7 Mb) and is non-recombinant with D3Mit346 (NCBI 36 position 116.1 Mb) and D3Mit57 (NCBI 36 position 115.8 Mb).

Pathology

A routine pathological screen of 44 tnyw/tnyw mutant mice from 16 days of age to 3.5 weeks of age was performed. There were vacuoles in the brain of all mutant mice (See Photo). Sections of thyroid glands, pituitary glands, and somatic organs revealed no abnormalities.

The eyes of 2 heterozygotes and 4 homozygotes were examined with an opthalamascope and the eyes of the heterozygotes were normal. The eyes of one of the 4 homozygotes had iris threads in the right eye and another mouse had a cataract in the right eye and the other two were normal. An abnormal lens was seen in four of the eyes. Slit lamp pictures show a suture cataract and lens is not round.

Hearing as assessed by auditory brainstem rsponse (ABR) testing on 2 mutants and 1 control revealed no hearing loss.

Acknowledgements

The authors thank Norm Hawes for the eye exminations and Chantal Longo-Guess for the hearing assessments.

The Jackson Laboratory