A New Hair Mutation Named Ruffled Maps to Chromosome 13
Belinda S. Harris, Patricia F. Ward-Bailey, Kenneth R. Johnson, 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: rul
Mutation (allele) name: ruffled
Gene symbol: rul
Strain of origin: RB156BNR/Ei
Current strain name: RB156BNR/Ei/J-rul/J
Stock #: 005362 (view JAX®Mice Data Sheet for additional information including Price and Supply Information)
Phenotype categories: skin and hair
Abstract
We have identified a new recessive mouse mutation that causes abnormal ruffled looking hair that can be classified at about 10 days of age. The mutation was mapped using an intercross with CAST/Ei and was found to be on Chromosome 13 at the 18 cM position.
Origin and Description
This mutation arose in the RB156/Bnr/EiJ strain in the Mouse Mutant Resource at The Jackson Laboratory in 1989 and was discovered by Belinda Harris. The phenotype of this mutation can be identified at about 10 days of age by a ruffled looking coat, which is different than the smooth coat of control littermates (See Photo). The hair of mutant mice is sparse and has some curling. The ruffled looking coat is maintained throughout the animal's lifespan, unlike the caracul and caracul-like mutants who lose some of their curly coat with age. Mice homozygous for the ruffled mutation have a normal lifespan and both sexes breed normally.
Genetic Analysis
This mutation was first identified as a recessive mutation by crossing an RB156BNR/Ei/J-rul/J mutant to an inbred C57BL/6JEi. 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 24 affected progeny of which 22 were used for linkage analysis. In order to avoid errors by misclassification, only animals with the most severe phenotype were used in the linkage analysis. The mutation maps on mouse Chromosome 13 between D13Mit60 (NCBIm33 position 35.3 Mb) and D13Mit19 (NCBIm33 position 43.2 Mb) and is non-recombinant with D13Mit18 (NCBIm33 position 35.6 Mb). Direct tests for allelism were set up by crossing a RB156BNR/Ei/J-rul/J mutant with hair mutants that have been mapped to Chromosome 13: furless (fs), juvenile alopecia (jal), and juvenile delipation (jd). The results showed 0 affected progeny out of 46 born in tests with fs, 0 affected progeny out of 17 born in tests with jal, and 0 affected progeny out of 32 born in tests with jd proving that all three of these Chr mutations are not allelic with ruffled. Before the map postion of rul/J was known, direct tests for allelism were set up by crossing a RB156BNR/Ei/J-rul/J mutant with each of the following known mutants: lancelate hair (lah) on Chr 18, fuzzy (fz) on Chr 1, waved 1(wa1) on Chr 6, waved 2 (wa2) on Chr 11, and frizzy (fr) on Chr 7. All were found not to be allelic.
Patholgy
A routine pathological screen done on two male mutants showed one with no lesions and the other animal had a severe cataract and mild hydrocephalus. Results of auditory brainstem response (ABR ) tests showed that homozygous mutant mice (N=12) and littermate heterozygous controls (N=6) have normal hearing up to ten weeks of age. At older ages, some hearing loss is observed in both mutant and control mice, likely an efffect of the strain background. Eyes were examined with an opthalmoscope and showed cataracts in both mutants and controls, which is characteristic of the RB156BNR/Ei strain background.
Discussion
A previously unknown hair mutation causing a sparse and ruffled coat has been identified and mapped to Chr 13 at the 18 cM position. The cause of this new mutation has not been determined.
Acknowledgements
The authors would like to thank Norm Hawes for examination of the eyes, Heping Yu for hearing assessment, and Coleen Marden excellent technical expertise.
References
Mouse Genome Database (MGD) Mouse Genome Informatics Project, The Jackson Laboratory, Bar Harbor, Maine. World Wide Web (2005)
(URL:http://www.informatics.jax.org)
MGSC27.33c.1. Mouse Genome Sequencing Consortium
(URL: http://www.ensembl.org/Mus_musculus/)
