title: Premature termination of hair follicle morphogenesis and accelerated hair follicle cycling in Iasi congenital atrichia (fzica) mice points to fuzzy as a key element of hair cycle control.
abstract: Inbred laboratory mice have proven to be useful model systems for studying hair biology and pathomechanisms of hair loss. Fuzzy (fz) is an autosomal recessive mutation that results in hair coat abnormalities. Though this mutant has long been known, its cutaneous abnormalities still await systematic analysis. Here, we provide a systematic skin phenotype analysis of mice that are homozygous for Iasi congenital atrichia (fzica/fzica), which is allelic to fz. Homozygous mice exhibit a sparse hair coat after birth and completely loose their hair at around postnatal day 120. Although early and mid stages of hair follicle morphogenesis are normal, late hair follicle morphogenesis reveals multifocal cell degeneration within the Huxley layer of the inner root sheath (IRS) and a complete lack of the hair shaft medulla. In addition, hair follicle development is prematurely terminated by induction of the first postnatal hair cycle with premature entry into catagen. Subsequently, a dramatically shortened telogen is immediately followed by premature anagen development, resulting in a marked, generalized acceleration of hair follicle cycling. This suggests that fuzzy is not only involved in structural hair shaft integrity and differentiation of the IRS and medulla, but also plays an important role in the control of hair follicle cycling. Our data show that fuzzy is involved in controlling both catagen and anagen initiation, designating fuzzy an exciting target for characterizing the intracutaneous oscillator system that drives hair follicle cycling.
authors: Department of Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4467, USA. l.mecklenburg@gmx.de
authors: Lars
authors: L
authors: Mecklenburg
authors: Desmond J
authors: DJ
authors: Tobin
authors: Marius V
authors: MV
authors: Cirlan
authors: Constantin
authors: C
authors: Craciun
authors: Ralf
authors: R
authors: Paus
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D006201:Hair Diseases / Q000235:genetics*; D018859:Hair Follicle / Q000473:pathology* / Q000502:physiology*; D006720:Homozygote; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009154:Mutation; D009991:Oscillometry; D010641:Phenotype; D011498:Protein Precursors / Q000378:metabolism; D013997:Time Factors
chemical_list: D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen; D011498:Protein Precursors; C016159:trichohyalin