A new spontaneous skin and hair mutation that causes a shiny and rough coat.

Richard Samples, Patricia F. Ward-Bailey, Linda L. Washburn, 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: Shar

Mutation (allele) name: Shiny and rough

Gene symbol: Shar

Strain of origin: C57BL/6J-Lbric-J/J

Current strain name: C57BL/6J-Shar/J

Stock #: 005482 (view JAX® Mice Data Sheet for additional information including Price and Supply Information) As of 11-21-06 available as cryoperserved or DNA.

Phenotype categories: skin and hair

Abstract

A new spontaneous dominant mutation affecting skin and hair has been identified and located on Chromosome 15. Mice heterozygous for the Shar mutation exhibit a shiny and rough coat that has a greasy appearance, and affected animals can be identified at 3 weeks of age. Shar maps to a region of Chr 15 where a cluster of other skin and hair mutations have been reported, however the phenotype and or chromosomal position of this mutation does not match those previously described (see below).

Origin and Description

The Shar mutation arose in the C57BL/6-Lbric-J/J strain and was discovered by Myrna Parker in 2000 in the Cryopreservation Recovery Department at The Jackson Laboratory. Mice carrying the Shar mutation exhibit a shiny and rough appearing coat (see photo) that resembles the previously described mouse mutation greasy (Gs) . However,  Gs is X linked whereas this new mutation is on Chr 15. The phenotype also resembles lustrous (lt) on Chr 11 and satin (Foxq1sa) on Chr 13, however the chromosomal location of this new mutation rules out allelism with these two mutations.  Shar/+ mice breed and live a normal lifespan.

Genetic Analysis

Using our standard mapping protocols , a backcross was set up to map this new mutation. A heterozygous C57BL/6J-Lbric-J/J female carrying this new mutation was mated to a CAST/Ei male. Mutant progeny from this cross were then backcrossed to an unrelated C57BL/6J +/+ mouse.  Fifty affected progeny were collected from this backcross and used for linkage analysis. 

The Shar mutation was mapped between D15Mit263 (at the 99.3 Mb NCBIm34 position) and D15Mit16 (at the 103.0 Mb NCBIm34 position). The keratin complex 2 (Krt2) extends from 101.5 - 102.1 Mb on Chr 15, and it is possible that Shar is a mutation of one of these keratin genes, which are known to underlie similar hair abnormalities. Other mouse skin and hair mutations that map to this region of Chr 15 include crimpy (cpy), caracul (Krt2-6gCa), Naked (N) shaven (Sha), and velvet coat (Ve). The recessive mutation crimpy (cpy) causes affected mice to have a wavy and rather plushy appearing coat and curly vibrissae (Lane 1992), which is not seen in Shar mutants. The dominant mutation caracul (Ca) causes a curly coat and curved vibrissae not seen in Shar mutants. Mice homozygous for the semidominant mutation naked (N) lack the appearance of a hair coat and vibrissae, while heterozygotes develop a first hair coat but lose it between 10-14 days of age (Sundberg,1994), whereas mice carrying the Shar mutation retain their hair and vibrissae and live a normal life span. Sha heterozygotes display a greasy coat similar to that observed in the Shar phenotype, but homozygotes are viable and exhibit sparse fur (Isaacson JH et al.1962. In contrast, Shar homozygotes appear to be embryonic lethal (see below) making allelism with shaven unlikely. Mutations in Ve affect ectoderm development causing homozygotes to die in utero (Rossant J; Vijh KM, 1981), whereas heterozygotes develop abnormal hair (Trigg MJ, 1972). The similarities in map positions and phenotypes suggest that Ve and Shar may be allelic; however, a direct test for allelism was not done because Ve is available only as cryoperserved embryos.

A special cross was set up to determine if C57BL/6-Shar/J homozygotes are dying in utero. C57BL/6-Shar/J mice were first mated to a C3H/HeSnJ mouse, and the resulting progeny were then intercrossed to produce F2s. The F2 progeny were typed by PCR for the closely linked markers D15Mit161 and D15Mit42, which flank the Shar mutation thereby permitting indirect determination of Shar genotypes. Of the 26 progeny typed from this cross, 2 animals were +/+ and the other 24 were heterozygotes. No homozygotes were seen, indicating that they may be dying in utero.

NOTE

The following paper shows that Ve is non-recombinant with Krt2:

Hart CP; Compton JG; Langley SH; Hunihan L; LeClair KP; Zelent A; Roderick TH; Ruddle FH, Genetic linkage analysis of the murine developmental mutant velvet coat (Ve) and the distal chromosome 15 developmental genes Hox-3.1, Rar-g, Wnt-1, and Krt-2., J Exp Zool 1992 Aug 1;263(1):83-95

Pathology 

Our standard pathological screen  of the somatic organs of two heterozygous mutants and two control littermates at 3 weeks of age showed no gross lesions. Pelt and hair samples taken from a 3 week old mutant and a control littermate showed that some hair follicles were dysplastic while others are normal in the mutant;samples from controls were normal. (See photo).

Hearing as assessed by auditory brainstem response (ABR) of two heterozygous mutants and two controls at 4 weeks of age was normal.

The eyes of three mutants and 1 control, all at 6 weeks of age, were examined with an opthalamscope and were determined to be normal.

Acknowledgements

The authors wish to thank Heping Yu for hearing assessment, Norman Hawes for examination of the eyes.  Ellen Akeson for PCR assays to determine the chromosomal location, and Coleen Marden for excellent technical skills.

References

Lane PW, "Crimpy (cpy) a new recessive hair mutation on Chromosome 15 of the mouse" Mouse Genome 1992;90(4):682-83.

Sundberg JP (Ed) Handbook of Mouse Mutations with Skin and Hair abnormalites,-Animal models and Biomedical Tools. CRC Press, Inc. 1994.

Isaacson JH et al., "Hfh11" Mouse News Lett 1962;27:31

Rossant J; Vijh KM, In vivo and in vitro development of mouse embryos homozygous for the embryonic lethal velvet coat (Ve) mutation., J Embryol Exp Morphol 1981 Dec;66():43-55.

Trigg MJ, Hair growth in mouse mutants affecting coat texture., J Zool 1972;168():165-198.