Association of a mutation in TRPV3 with defective hair growth in rodents.
DS-Nh mice and WBN/Kob-Ht rats are spontaneous hairless mutant rodent strains. These animals develop spontaneous dermatitis under normal conditions. The non-hair Nh and Ht phenotypes are inherited in an autosomal dominant fashion, and the Nh mutation possesses a high potency for penetration. We previously reported that genes involved in dermatitis and hairlessness did not segregate from each other. Here, we carried out genetic analysis to identify the genes responsible for these hairless mutations. An amino-acid substitution at the same position in one gene was detected in DS-Nh mice and WBN/Kob-Ht rats: Gly573 to Ser (Nh mutation) or Gly573 to Cys (Ht mutation), located in the transient receptor potential (TRP) cation channel subfamily V member 3 (TRPV3) gene. Mutated TRPV3 was expressed in skin keratinocytes of DS-Nh mice. Histopathological analyses revealed that mast cells in skin lesions were increased in both rodents compared to their age-matched parent strains, and that this may partially be due to hairlessness and dermatitis. We concluded that TRPV3 was the gene responsible for Nh and Ht mutations, and that mutation in TRPV3 possibly correlated with increased mast cell numbers.
Asakawa
Makoto
M
Shionogi Discovery Research Laboratories, Shionogi & Co., Ltd, Osaka, Japan.
Yoshioka
Takeshi
T
Matsutani
Takaji
T
Hikita
Ichiro
I
Suzuki
Minoru
M
Oshima
Itsuki
I
Tsukahara
Kiyoshi
K
Arimura
Akinori
A
Horikawa
Tatsuya
T
Hirasawa
Tsutomu
T
Sakata
Tsuneaki
T
D000505:Alopecia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019943:Amino Acid Substitution; D000818:Animals; D002452:Cell Count; D003001:Cloning, Molecular; D003545:Cysteine; D003872:Dermatitis / Q000235:genetics / Q000378:metabolism; D004594:Electrophysiology; D005998:Glycine; D006632:Histamine / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D051381:Rats; D011923:Rats, Nude; D012694:Serine; D012867:Skin / Q000378:metabolism / Q000473:pathology; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism
D050916:TRPV Cation Channels; C505767:TRPV3 protein, rat; C486760:Trpv3 protein, mouse; D012694:Serine; D006632:Histamine; D003545:Cysteine; D005998:Glycine