Phenotype Image Detail

Image

Caption

Structural and ultrastructural analyses showing that UVB-mediated skin tissue injury depends upon keratinocyte TRPV4. (A) Toluidine blue semithin (1-um) sections. Micrographs show representative findings of skin in response to UVB, sampled 48 h after UVB exposure. Note that upon UVB stimulation oil- (TRPV+), but not tamoxifen (tam)-treated (TRPV-), Trpv4^tm1.1Ldtk/Trpv4^tm1.1Ldtk Tg(KRT14-cre/ERT)20Efu/0 (iKO) mice exhibit separations at the epidermal-dermal boundary and robust signs of tissue injury including influx of neutrophil granulocytes. Note also that just beneath the stratum corneum (SC) the upper epidermis shows extensive structural damage, which could also be seen in skin of tam-treated iKO mice in which Trpv4 knockdown was incomplete, but not in those animals in which it was more complete. (Scale bars, 20 um.) Der, dermis; Epi, epidermis. (B) Ultrastructural findings by EM. Selected areas from 1-um semithin sections of paw skin were examined by transmission electron microscopy. a and a' and c and c' show normal epidermal (Epi) structure for both oil- and tam-treated iKO mice, in the absence of UVB stimulation. a and c show an intact epidermis. Basal (BL) and spinous (Sp) layers are magnified a' and c' displaying a normal organization with no evidence of epidermal damage. b, b', b", d, d', and e, e' show representative findings of skin in response to UVB, sampled 48 h after UVB exposure. (b) Disrupted epidermis in oil-treated iKO mice. An area equivalent to the boxed area is magnified in b', where granulocyte infiltration of epidermis is evident (Gr) and blistering with detachment of the epidermis from the dermis (double arrows). (b") Upper part of epidermis in contact with SC, showing extensive vacuolization and deposits of fibrin inside the vacuoles (asterisks). (d) Tamoxifen-treated iKO mice with incomplete knockdown of Trvp4 show skin phenotype similar to oil-treated iKO mice, with robust signs of tissue damage to basal and spinous layer, fibrin deposits (asterisks), and intercellular spaces (arrowheads in d'). (e) Intact epidermis in iKO with complete knockdown of Trvp4, with normal basal and spinous layers in e'. Dotted lines indicate the dermal-epidermal boundary. (Scale bars, 20 um for a, b, c and d; 10 um for b' and e', and 2 um for the other micrographs.)

Copyright

This image is from Moore C, Proc Natl Acad Sci U S A 2013 Aug 20;110(34):E3225-34. Copyright 2013 National Academy of Sciences, U.S.A. J:200749

Associated Alleles

Symbol	Name
Tg(KRT14-cre/ERT)20Efu	transgene insertion 20, Elaine Fuchs
Trpv4^tm1.1Ldtk	transient receptor potential cation channel, subfamily V, member 4; targeted mutation 1.1, Wolfgang Liedtke

Associated Genotypes

Allelic Composition	Genetic Background
Trpv4^tm1.1Ldtk/Trpv4^tm1.1Ldtk Tg(KRT14-cre/ERT)20Efu/0	involves: C57BL/6 * CD-1 * SJL