These mice carry a spontaneous mutation at the Sfn locus characterized by progressive and repetitive hair loss along with other morphological abnormalities.Read More +
This mutation shows complete penetrance in heterozygotes. These mice grow a normal appearing but probably somewhat dry first coat until the age of about 13 days; then hair loss begins and continues until the fur becomes sparse. Repeated growth and re-epilation follow without a definite pattern. Heterozygotes are slightly reduced in size and some may die before weaning, but adults are fully viable and fertile. Homozygotes die at birth from inability to breathe because of a closed oral cavity. At embryonic day 17 the skin of homozygotes is extremely thin and smooth with few vibrissae and hair follicles. The snout is truncated and the mouth closed. The limbs and tail are greatly shortened and held close to the trunk and the anal and urogenital orifices are closed. There are marked skeletal abnormalities and cleft palate. Homozygotes can be recognized at 13 days of gestation by their blunt limbs and stumpy tail. Between 13 and 15 days the nares and oral opening close, resulting in marked compression and abnormality of the structures in the area. Heterozygotes are recognizable at 18 days of gestation by edema of the feet and hemorrhagic tail tip. Histologically, at 19 days of gestation, skin of heterozygotes does not differ from +/+ skin. Skin of homozygotes is characterized by wide intercellular spaces and highly variable numbers and distribution of cells of the spinous, granular, and superficial layers. A 26.5 kDa protein, filaggrin, is absent, but filaggrin precursors appear to be present. In heterozygotes there is a high incidence of multiple cutaneous papillomas and squamous cell carcinomas.
The repeated epilation mutation arose in a random bred stock at Oak Ridge National Laboratory in approximately 1960 and was subsequently imported into The Jackson Laboratory for Dr. George Snell. Dr. Snell passed this mutation to Dr. Don Bailey who maintained this dominant mutation by continuous backcrossing to C57BL/6By. Dr. Bailey later transferred this congenic strain to Dr. Eva Eicher and in 1983 the breeding scheme changed to crossing a heterozygote to a (C57BL/6J-Aw-J/J x CBA/CaGnLeJ)F1 hybrid at each generation. In 1984 embryos were generated for cryopreservation from C57BL/6J females bred with B6CBACa Aw-J/A-SfnEr/J heterozygous males at generation N3F1.
|Allele Name||repeated epilation|
|Allele Type||Radiation induced|
|Gene Symbol and Name||Sfn, stratifin|
|Strain of Origin||Not Specified|
|General Note||Sfn is on Chr 4 close to pupoid fetus (pf), a mutant which SfnEr closely resembles.|
|Molecular Note||A single T insertion at base pair 622 causes a frame shift mutation at amino acid residue 207 truncating the C-terminus of the protein. This eliminates residues required for ligand interaction. Production of truncated protein was demonstrated immunologically. The hair-loss phenotype could be rescued using a Sfn containing transgene.|