Follicular dystrophy: a new skin and hair mutation on mouse Chromosome 2
Belinda S. Harris, Patricia F. Ward-Bailey, Kenneth R. Johnson, and Roderick T. Bronson
Source of Support: The 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: fold
Mutation (allele) name: follicular dystrophy
Gene symbol: fold
Strain of origin: P/J
Current strain name: B6Ei.P-fold/J
Stock #: 006449 (View JAX®Mice Data Sheet for additional information including Price and Supply Information)Phenotype categories: skin and hair, size
Abstract
A new spontaneous autosomal recessive hair mutation named follicular dystrophy (fold) has been found at The Jackson Laboratory in a production colony of P/J mice. Mice homozygous for the fold mutation have a smaller body size than littermate controls and can be characterized by a lack of visible hair at one week of age and by wrinkled skin by two weeks of age. F2 progeny generated by a linkage cross to CAST/Ei were utilized to map the follicular dystrophy mutation to Chromosome 2.
Origin and Description
Throughout their relatively short lifespan, mice homozygous for the fold mutation have a body size that is smaller than normal littermates. Mutants of both sexes exhibit shortened lifespans; most die at three weeks of age and to date, no homozygote has lived long enough to breed. Hair is not visible by one week of age (See Photo) but some hair does grow in to give the appearance of a sparse coat by weaning age at three weeks. (See photo) At two weeks of age the skin is noticeably wrinkled. This colony is maintained by progeny testing to produce heterozygous pairs or by ovarian transplants performed on homozygous females, which then are mated to C57BL6/JEi males. The current generation is F73 + N4 to C57BL/6JEi .
Genetic Analysis
The recessive inheritance of the follicular dystrophy mutation was determined by mating a female CAST/Ei to a male heterozygote fold/+. This mating produced no mutants out of eleven progeny born in the F1 generation. Using our standard mapping protocols, an intercross of tested F1s from the previous mating did produce the mutant phenotype in the F2 generation confirming recessive inheritance. This intercross produced 52 F2 mutant progeny that were used to map fold to Chromosome 2. The fold mutation mapped between D2Mit64 (NCBIm36 position 31.1 MB) and D2Mit522 (position 32.7-32.9 MB).
Pathology
Eleven homozygous follicular dystrophy mice were sent to pathology for a routine pathological screen and were found to have dermatitis and degeneration of the testis in one male. Others had dysplastic hair follicles (See photo).The follicular dystrophy seen was the hair follicle not producing a normal hair fiber.
Hearing as assessed by Auditory Brainstem Response (ABR) testing of two homozygous fold/fold mice and one control littermate was normal.Eyes of two mutants and controls were examined using an opthalmascope and found to have normal iris, lens and retinas.
Discussion
The new follicular dystrophy mutation maps near two similar skin and hair mutations, wrinkle-free (Slc27a4wrfr) (NCBIm36 position 29.7 MB) and a targeted null mutation in the integrin beta 6 (Itgb6) gene (NCBIm36 position 60.3-60.5 . However both of these genes are outside of the critical region for the fold mutation.To date no other skin and hair mutations are mapped to the fold region.
Acknowledgements
The authors wish to thank Dr. John Sundberg and Dawnalyn Boggess for initial workup of this mutation, Arcel Dullas and Lori Whitney for the original discovery of this new mutation, Heping Yu for ABR testing, Coleen Marden for skeletal and pathological preparations, and Leona Gagnon for photography.
References
Casey L. Moulson, Daniel R. Martin, Jesse J. Lugus, Jean E. Schaffer, Anne C. Lind, and Jeffrey H. Miner. Cloning of wrinkle-free, a previously uncharacterized mouse mutation, reveals crucial roles for fatty acid transport protein 4 in skin and hair development. PNAS | April 29, 2003 | vol. 100 | no. 9 | 5274-5279
