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J. Biol. Chem., Vol. 277, Issue 19, 17147-17153, May 10, 2002
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From the The water and solute transporting
properties of the epidermis have been proposed to be important
determinants of skin moisture content and barrier properties. The
water/small solute-transporting protein aquaporin-3 (AQP3) was found by
immunofluorescence and immunogold electron microscopy to be expressed
at the plasma membrane of epidermal keratinocytes in mouse skin. We
studied the role of AQP3 in stratum corneum (SC) hydration by
comparative measurements in wild-type and AQP3 null mice generated in a
hairless SKH1 genetic background. The hairless AQP3 null mice had
normal perinatal survival, growth, and serum chemistries but were
polyuric because of defective urinary concentrating ability. AQP3
deletion resulted in a >4-fold reduced osmotic water permeability and
>2-fold reduced glycerol permeability in epidermis. Epidermal, dermal,
and SC thickness and morphology were not grossly affected by AQP3
deletion. Surface conductance measurements showed remarkably reduced SC
water content in AQP3 null mice in the hairless genetic background
(165 ± 10 versus 269 ± 12 microsiemens
(µS), p < 0.001), as well as in a CD1 genetic
background (209 ± 21 versus 469 ± 11 µS).
Reduced SC hydration was seen from 3 days after birth. SC hydration in hairless wild-type and AQP3 null mice was reduced to comparable levels
(90-100 µS) after a 24-h exposure to a dry atmosphere, but the
difference was increased when surface evaporation was prevented by
occlusion or exposure to a humidified atmosphere (179 ± 13 versus 441 ± 34 µS). Conductance measurements after serial tape stripping suggested reduced water content throughout the SC
in AQP3 null mice. Water sorption-desorption experiments indicated
reduced water holding capacity in the SC of AQP3 null mice. The
impaired skin hydration in AQP3 null mice provides the first functional
evidence for the involvement of AQP3 in skin physiology. Modulation of
AQP3 expression or function may thus alter epidermal moisture content
and water loss in skin diseases.
Impaired Stratum Corneum Hydration in Mice Lacking Epidermal
Water Channel Aquaporin-3*
§,¶,
,, and
Departments of Medicine and Physiology,
Cardiovascular Research Institute, University of California, San
Francisco, California 94143-0521, ¶ Basic Research Laboratory,
Kanebo Ltd., Odawara 250-0002, Japan, and Service de
Biologie Cellulaire, CEA, F-91191 Saclay, France
*
This work was supported by Grants DK35124, DK43840, EB00415,
EY13574, HL60288, and HL59198 from the National Institutes of Health, a
grant from the Cystic Fibrosis Foundation, a gift from Kanebo, Ltd. of
Japan, and Contract ERBFMRXCT97-0128.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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