title: Impact of the Gly573Ser substitution in TRPV3 on the development of allergic and pruritic dermatitis in mice.
abstract: We reported that the Gly573Ser substitution in transient receptor potential vanilloid 3 (TRPV3) led to increased ion channel activity in keratinocytes and caused spontaneous hairlessness in DS-Nh mice. DS-Nh mice also develop allergic and pruritic dermatitis. As the hairless and dermatitis phenotypes were both inherited in an autosomal dominant fashion and could not be segregated from each other, we speculated that TRPV3(Gly573Ser) might be responsible for the dermatitis. Here, we constructed TRPV3(Gly573Ser) transgenic mice, with a putative promoter sequence in the 5' region of TRPV3, to investigate the involvement of TRPV3 in the development of specific types of dermatitis. These transgenic mice spontaneously developed dermatitis, whereas wild-type mice did not display this phenotype when maintained under the same conditions. Histological and serological analyses were carried out to better understand the clinical features of TRPV3(Gly573Ser) transgenic mice. A physiological study revealed that TRPV3(Gly573Ser) induced a higher nerve growth factor response to heat. Finally, C57BL-Nh mice were used to investigate the penetrance of the TRPV3(Gly573Ser) gene for dermatitis. Interestingly, C57BL-Nh mice developed spontaneous scratching behavior, separately from the development of dermatitis. We propose that TRPV3(Gly573Ser) is a cause of pruritus and/or dermatitis associated with scratching, and suggest that TRPV3 may represent a therapeutic target in pruritic dermatitis.
authors.affiliation: Shionogi Discovery Research Laboratories, Shionogi and Co. Ltd, Osaka, Japan. takeshi.yoshioka@shionogi.co.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Kinichi
authors.initials: K
authors.lastname: Imura
authors.forename: Makoto
authors.initials: M
authors.lastname: Asakawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Suzuki
authors.forename: Itsuki
authors.initials: I
authors.lastname: Oshima
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hirasawa
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Sakata
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Horikawa
authors.forename: Akinori
authors.initials: A
authors.lastname: Arimura