Severe Runting (sevr): A New Mouse Mutation on Chromosome 18
Belinda Harris, Patricia F. Ward-Bailey, Roderick T. Bronson, Kenneth Johnson, and Muriel T. Davisson
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: sevr
Mutation (allele) name: severe runting
Gene symbol: sevr
Strain of origin: C3H/HeJ
Current strain name: C3H/HeJ-sevr/J
Stock #: 006247 (view JAX® Mice Data Sheet for additional information including Price and Supply Information)
Phenotype categories: size, skeletal
Abstract
A new autosomal recessive mutation has been identified and named severe runting (sevr). This mutation when homozygous causes a reduced body size, slight tremors, and a shortened lifespan with many animals dying by weaning. This mutation maps to Chromosome 18.
Origin and Description
This new mutation arose in a colony of inbred C3H/HeJ mice in the Mouse Mutant Resource at The Jackson Laboratory in 1998 and was discovered by Karen Smith. The sevr mutants were first observed because of their unusually small size. Homozygotes are characterized at about two weeks of age as having a smaller body size than their littermates (See Photo) and by a high mortality rate at approximately four weeks of age. Slight tremors in homozygotes are often observed before death. The sevr colony is maintained by progeny tests and heterozygous pairs produce close to the expected 25% homozygotes.
Genetic Analysis
Using our standard mapping procedures an intercross was set up by mating two female CAST/Ei mice to a male heterozygous for the severe runting mutation. No affected mutant mice were observed in the 51 progeny produced by this cross. The tested heterozygous F1 progeny from this cross were then intercrossed and in four matings produced 47 affected progeny out of 485 total born for 9.7% expression (less than the expected 25%). Using standard PCR techniques and DNA from 33 F2 progeny from the previous cross for linkage analysis, the severe runting mutation was mapped to Chromosome 18. This new mutation maps distal to D18Mit51 (NCBIm36 position 61.2 MB), proximal to D18Mit40 (NCBIm36 position 63.9 MB), and is non-recombinant with D18Mit139 (NCBIm36 position 62.5 MB). To date no other mutations causing a similar phenotype have been mapped to this region.
Pathology
A standard pathological screen of 9 mutant mice between 5 weeks and 4 months of age showed atrophy of the thymus which is typical of wasting mice, and no other consistant lesions.
Hearing was assessed by auditory brain stem response (ABR) testing of one homozygote and one heterozygote at 35 days of age and two mutants and two controls at 25 days of age. All mutant and control mice had normal ABR thresholds indicating good hearing.
The eyes of two mutant and two control animals at 3 weeks of age were examined with an opthalmoscope and they were determined to be normal for their age.
Histology was done on the eyes of one homozygous mutant and they were normal except that they have retinal degeneration 1 (rd-1), which is a characteristic of the C3H background strain and not caused by this new mutation.
Acknowledgements
The authors would like to thank Norm Hawes for the eye examinations, Heping Yu and Chantal Longo-Guess for hearing assessment, Coleen Marden for histological techniques, and Leona Gagnon for photographic assistance.
