Targeted deletion of Atg5 reveals differential roles of autophagy in keratin K5-expressing epithelia

Journal Article · Fri Jan 11 04:00:00 EST 2013 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2012.11.090· OSTI ID:22210385

Sukseree, Supawadee ^[1]; Rossiter, Heidemarie; Mildner, Michael ^[1]; Pammer, Johannes ^[2]; Buchberger, Maria; Gruber, Florian ^[1]; Watanapokasin, Ramida ^[3]; Tschachler, Erwin ^[1]; Eckhart, Leopold ^[1]

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1. Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna (Austria)
2. Institute of Clinical Pathology, Medical University of Vienna, Vienna (Austria)
3. Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok (Thailand)

Highlights: Black-Right-Pointing-Pointer We generated mice lacking Atg5 and autophagy in keratin K5-positive epithelia. Black-Right-Pointing-Pointer Suppression of autophagy in thymic epithelium was not associated with signs of autoimmunity. Black-Right-Pointing-Pointer Autophagy was required for normal terminal differentiation of preputial gland cells. Black-Right-Pointing-Pointer Autophagy-deficient cells of the preputial glands degraded nuclear DNA prematurely. -- Abstract: Autophagy contributes to the homeostasis of many tissues, yet its role in epithelia is incompletely understood. A recent report proposed that Atg5-dependent autophagy in thymic epithelial cells is essential for their function in the negative selection of self-reactive T-cells and, thus, for the suppression of tissue inflammation. Here we crossed mice carrying floxed alleles of the Atg5 gene with mice expressing the Cre recombinase under the control of the keratin K5 promoter to suppress autophagy in all K5-positive epithelia. The efficiency of autophagy abrogation was confirmed by immunoanalyses of LC3, which was converted to the autophagy-associated LC3-II form in normal but not Atg5-deficient cells, and of p62, which accumulated in Atg5-deficient cells. Mice carrying the epithelium-specific deletion of Atg5 showed normal weight gain, absence of tissue inflammation, and a normal morphology of the thymic epithelium. By contrast, autophagy-deficient epithelial cells of the preputial gland showed aberrant eosinophilic staining in histology and premature degradation of nuclear DNA during terminal differentiation. Taken together, the results of this study suggest that autophagy is dispensable for the suppression of autoimmunity by thymic epithelial cells but essential for normal differentiation of the preputial gland in mice.

• OSTI ID: 22210385
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 430; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
DNA
EOSIN
EPITHELIUM
FLUORESCENCE
GLANDS
HEMATOXYLIN
HISTOLOGY
HOMEOSTASIS
INFLAMMATION
INHIBITION
KERATIN
LABELLING
MICE
MICROTUBULES
POLYMERASE CHAIN REACTION
PROMOTERS
THYMUS
TRANSCRIPTION