Disturbed Keratinocyte Differentiation in Transgenic Mice and Organotypic Keratinocyte Cultures as a Result of Spermidine/Spermine N1-Acetyltransferase.

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Disturbed Keratinocyte Differentiation in Transgenic Mice and Organotypic Keratinocyte Cultures as a Result of Spermidine/Spermine N1-Acetyltransferase Overexpression Marko Pietilä, Eija Pirinen, Salla Keskitalo, Sisko Juutinen, Sanna Pasonen-Seppänen, Tuomo Keinänen, Leena Alhonen, Juhani Jänne Journal of Investigative Dermatology Volume 124, Issue 3, Pages 596-601 (March 2005) DOI: 10.1111/j.0022-202X.2005.23636.x Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Localization of K14, K1/10, filaggrin, K6, and proliferating cell nuclear antigen (PCNA) in mouse skin and organotypic cultures. (A) Skin sections of wild-type (Wt) and spermidine/spermine N1-acetyltransferase (SSAT) transgenic (Tg) mice were immunostained with antibodies against cytokeratins 14, 1/10, filaggrin, cytokeratin 6, and PCNA, as indicated. Note the abundant immunostaining of K14 in cornified layer in Tg skin and the downregulation of K1/10 and filaggrin. Regardless of a high number of PCNA positive cells, no K6 expression can be seen at the interfollicular epidermis of Tg mice. (B) The effect of 0.5%α-difluromethylornitine (DFMO) on K 14 expression and hair follicle activation after 2 wk treatment. Note the normalization of epidermis seen as downregulation of K14 (greater magnification in the upper right corner) and the appearance of K14-negative cells in the middle of the dermal cysts. (C) Hematoxylin–eosin and immunostained sections of organotypic cultures derived from SSAT Tg clones (SSAT 1–5) and a control clone transfected only with selection marker. Note the persisting immunostaining of K14 form the basal cell to more superficial layers and the clearance of K10 and filaggrin in the clones SSAT 2–5. Scale bar=25 μm. Journal of Investigative Dermatology 2005 124, 596-601DOI: (10.1111/j.0022-202X.2005.23636.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Reduction of putrescine reactivates the hair growth. Two spermidine/spermine N1-acetyltransferase transgenic littermates are presented. The mouse in front has been treated with 0.5% (wt/vol) α-difluromethylornitine in drinking water for 4 wk whereas the mouse in the back belonged to the control group receiving plain tap water. Note the newly formed hair on the back of the treated animal. Journal of Investigative Dermatology 2005 124, 596-601DOI: (10.1111/j.0022-202X.2005.23636.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions