Short term perm (stpm): a new recessive curly coat mutation

Richard M. Samples, Patricia F. Ward-Bailey, Leah Rae Donahue, Roderick T. Bronson, 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:stpm

Mutation (allele) name: short term perm

Gene symbol: stpm

Strain of origin: RHJ/LeJ/J

Current strain name: RHJ/LeJ-stpm/J

Stock #:005415 (view JAX® Mice Data Sheet for additional information including Price and Supply Information)

Phenotype categories: Hair

Abstract

We have identified a new recessive mutation that causes a curly coat and have named it short term perm (stpm). Mutant mice can be identified at 8 days of age, with the first coat of fur. The mutation was mapped using an intercross to CAST/Ei and was found to be on Chromosome 11 near a previously described dominant curly coat mutation named Rex (Re) (MGD 2005). A direct test for allelism between mice carrying the Rex mutation and mice carrying this new mutation was negative. Another mutation causing an eye phenotype has been identified in this strain and will be described in a future publication.

Origin and Description

This new recessive mutation arose spontaneously in a breeding colony of RHJ/LeJ mice at The Jackson Laboratory and was discovered by Suzanne Sullivan. The phenotype of this mutation can be identified by a curly coat, which is different from the smooth coat of control littermates (See Photo). At 3 weeks of age, mice homozygous for this new mutation have very curly coats and slightly curved vibrissae. In several weeks time the curly coat disappears but the hair retains a rough texture, and the vibrissae then appear normal (See Photo). Heterozygous mice have normal smooth coats and straight whiskers. The RHJ/LeJ strain carries Rhino  (Hrrh), an allele of the hairless mutation. This mutation has been bred out of the  the RHJ/LeJ-stpm/J strain. Both male and female mutant mice breed and live a normal lifespan.

Genetic Analysis

This mutation was first identified as a recessive mutation by crossing an RHJ/LeJ-stpm/J mutant to an inbred C57BL/6Ei/J. In this cross no mutants were produced in the F1 generation, but mutants were produced in the F2 intercross generation. Using our standard mapping procedures  an intercross with CAST/Ei was set up and generated 36 affected progeny that were used for linkage analysis. The mutation maps on mouse Chromosome 11 between D11Mit285 (NCBIm33 position 89.7 Mb) and D11Mit224 (NCBIm33 position 108.3 Mb) and is non-recombinant with D11Mit59 (NCBIm33 position 99.9 Mb).

Based on the phenotype and map position similarity of this new mutation to the previously described Rex (Re) mutation, a direct test for allelism was set up by mating a mouse homozygous for the stpm mutation to a mouse homozygous for the Re mutation. When homozygous, the dominant Rex gene causes a curlier coat than when it is heterozygous. This curlier coat was not seen in the offspring produced in the test for allelism, indicating that the new mutation is not likely a remutation of Re.

Pathology

A routine pathological screen done on two mutants and two control littermates at 7 weeks of age showed no lesions in somatic organs. Hair samples and pelt pads taken at 4 and 5 weeks of age showed that the skin is histologically normal. There is a normal distribution of hair types present in affected animals, but the zigzag hairs have abnormal bends and kinks. A few of the zigzag hairs have variable thickness and guard hairs are rare. (See Photo)

Hearing as accessed by auditory brainstem response (ABR) on three mutant mice and two controls was normal.

Discussion

A previously unknown curly coat mutation has been identified and mapped to Chromosome 11 at the 58.5 cM position. The cause of this new mutation has not been determined. Besides Re, 5 other skin and hair mutations, bareskin (Bsk), reduced coat 2  (Rco2), defolliculated(Dfl),  finnegan (Fgn), and Rex denuded Re<den> (all mutations in the gasdermin 3 gene, map in this region of Chr 11.  These mutations are phenotypically different when compared to stpm mutants.  BSk is a dominant ENU induced mutation that causes alopecia beginning at 3 weeks and then thick, wrinkled skin.  Rco2  is a dominant ENU induced mutation that causes mutants to have a normal coat for 3 weeks, followed by a sparse second coat, and are hairless (except on the face) by 6 months of age. Dfl is a spontaneous dominant mutation that causes alopecia between 3 and 4 weeks of age and mutants develop thick, folded skin. Fgn is a dominant ENU induced mutation that causes alopecia at 6 weeks of age. Gsdm3<Re-den> is a spontaneous, semidominant mutation  that causes affected animals to begin having alopecia at 3 weeks and develop thick, wrinkled skin. Another candidate gene in this region is keratin gene complex 1, acidic (Krt1) which is involved in hair follicle development. Tests for allelism were not performed with the Gsdm 3 mutations, because the mutations are available as cryopreserved only. Sequencing of the Gsdm 3 gene in search of the stpm mutation was not done. A test for allelism was not done for Krt1 because the mice are not available.

Acknowledgements

The authors wish to thank Suzanne Sullivan for the discovery of the mutant, Coleen Marden for her excellent technical assistance, and Heping Yu for hearing assessment.

References

 MGD 2005

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