Targeted skin overexpression of the mineralocorticoid receptor in mice causes epidermal atrophy, premature skin barrier formation, eye abnormalities, and alopecia

Yannis Sainte Marie, Antoine Toulon, Ralf Paus, Eve Maubec, Aicha Cherfa, Maggy Grossin, Vincent Descamps, Maud Clemessy, Jean Marie Gasc, Michel Peuchmaur, Adam Glick, Nicolette Farman, Frederic Jaisser

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The mineralocorticoid receptor (MR) is a transcription factor of the nuclear receptor family, activation of which by aldosterone enhances salt reabsorption in the kidney. The MR is also expressed in nonclassical aldosterone target cells (brain, heart, and skin), in which its functions are incompletely understood. To explore the functional importance of MR in mammalian skin, we have generated a conditional doxycycline-inducible model of MR overexpression, resulting in double-transgenic (DT) mice [keratin 5-tTa/tetO-human MR (hMR)], targeting the human MR specifically to keratinocytes of the epidermis and hair follicle (HF). Expression of hMR throughout gestation resulted in early postnatal death that could be prevented by antagonizing MR signaling. DT mice exhibited premature epidermal barrier formation at embryonic day 16.5, reduced HF density and epidermal atrophy, increased keratinocyte apoptosis at embryonic day 18.5, and premature eye opening. When hMR expression was initiated after birth to overcome mortality, DT mice developed progressive alopecia and HF cysts, starting 4 months after hMR induction, preceded by dystrophy and cycling abnormalities of pelage HF. In contrast, interfollicular epidermis, vibrissae, and footpad sweat glands in DT mice were normal. This new mouse model reveals novel biological roles of MR signaling and offers an instructive tool for dissecting nonclassical functions of MR signaling in epidermal, hair follicle, and ocular physiology.

Original languageEnglish (US)
Pages (from-to)846-860
Number of pages15
JournalAmerican Journal of Pathology
Volume171
Issue number3
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

Fingerprint

Eye Abnormalities
Mineralocorticoid Receptors
Alopecia
Atrophy
Hair Follicle
Skin
Transgenic Mice
Aldosterone
Keratinocytes
Epidermis
Ocular Physiological Phenomena
Keratin-5
Vibrissae
Sweat Glands
Doxycycline
Cytoplasmic and Nuclear Receptors
Nuclear Family
Cysts
Transcription Factors
Salts

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Targeted skin overexpression of the mineralocorticoid receptor in mice causes epidermal atrophy, premature skin barrier formation, eye abnormalities, and alopecia. / Marie, Yannis Sainte; Toulon, Antoine; Paus, Ralf; Maubec, Eve; Cherfa, Aicha; Grossin, Maggy; Descamps, Vincent; Clemessy, Maud; Gasc, Jean Marie; Peuchmaur, Michel; Glick, Adam; Farman, Nicolette; Jaisser, Frederic.

In: American Journal of Pathology, Vol. 171, No. 3, 01.01.2007, p. 846-860.

Research output: Contribution to journalArticle

Marie, YS, Toulon, A, Paus, R, Maubec, E, Cherfa, A, Grossin, M, Descamps, V, Clemessy, M, Gasc, JM, Peuchmaur, M, Glick, A, Farman, N & Jaisser, F 2007, 'Targeted skin overexpression of the mineralocorticoid receptor in mice causes epidermal atrophy, premature skin barrier formation, eye abnormalities, and alopecia', American Journal of Pathology, vol. 171, no. 3, pp. 846-860. https://doi.org/10.2353/ajpath.2007.060991
Marie, Yannis Sainte ; Toulon, Antoine ; Paus, Ralf ; Maubec, Eve ; Cherfa, Aicha ; Grossin, Maggy ; Descamps, Vincent ; Clemessy, Maud ; Gasc, Jean Marie ; Peuchmaur, Michel ; Glick, Adam ; Farman, Nicolette ; Jaisser, Frederic. / Targeted skin overexpression of the mineralocorticoid receptor in mice causes epidermal atrophy, premature skin barrier formation, eye abnormalities, and alopecia. In: American Journal of Pathology. 2007 ; Vol. 171, No. 3. pp. 846-860.
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