Inhibition of retinoid signaling in transgenic mice alters lipid processing and disrupts epidermal barrier function

Molecular Endocrinology
P S AttarD R Roop

Abstract

To explore the role of retinoids in epidermal development, we recently targeted expression of a dominant-negative, retinoic acid receptor mutant (RAR alpha403) in the epidermis of transgenic mice and observed an unexpected loss of barrier function. In this paper, we demonstrate that transgenic mice expressing the RAR alpha403 transgene show attenuated responsiveness to topical application of all-trans retinoic acid, in agreement with our previous in vitro data. We also show that the vitamin D3 receptor is unaffected in its ability to transactivate in the presence of the dominant-negative RAR alpha403 transgene, indicating that the RAR alpha403 is unlikely to be functioning through a global sequestration of retinoid X receptors. Additionally, we show that the disruption of epidermal barrier function results in a dramatic 4 C drop in mean body surface temperature, probably accounting for the extremely high incidence of neonatal mortality in severely phenotypic pups. Some severely affected pups do survive and show a pronounced hyperkeratosis at postpartum day 4, consistent with previously documented effects of vitamin A deficiency. Biochemical analysis of the severely phenotypic neonates indicates elevated phospholipids and glycos...Continue Reading

Citations

Aug 23, 2011·PloS One·Laura García-SerranoAna Aranda
Jul 26, 2003·The Journal of Investigative Dermatology·Kathi C Madison
Jul 18, 2008·Experimental Dermatology·György ParaghGerd Schmitz
Sep 15, 2011·Biochimica Et Biophysica Acta·Helen B Everts
Apr 2, 2005·Nature Reviews. Molecular Cell Biology·Eleonora CandiGerry Melino
Jun 1, 2007·Molecular Carcinogenesis·Satish B CheepalaJohn L Clifford
Mar 29, 2020·International Journal of Molecular Sciences·Yosuke Ishitsuka, Dennis R Roop
Dec 4, 2020·Tissue Barriers·Yosuke IshitsukaTatsuya Ogawa
Oct 3, 1998·The Journal of Biological Chemistry·M A RogersJ Schweizer
Nov 6, 2004·The Journal of Biological Chemistry·Chang Feng Chen, David Lohnes
Sep 1, 2020·Dermatology : International Journal for Clinical and Investigative Dermatology·Renata LucasRalph Rühl

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