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Molecular and Cellular Biology, January 2006, p. 548-558, Vol. 26, No. 2
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.2.548-558.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Elimination of Epiplakin by Gene Targeting Results in Acceleration of Keratinocyte Migration in Mice

Mizuki Goto,¹ Hideaki Sumiyoshi,¹ Takao Sakai,² Reinhard Fässler,² Shihoka Ohashi,³ Eijiro Adachi,³ Hidekatsu Yoshioka,¹ and Sakuhei Fujiwara^1*

Department of Anatomy, Biology and Medicine (Dermatology and Biochemistry), Faculty of Medicine, Oita University, Hasama-machi, Yufu 879-5593, Japan,¹ Department of Molecular Medicine, Max Planck Institute for Biochemistry, 82152 Martinsried, Germany,² Department of Molecular Morphology, Kitasato University Graduate School of Medicine, Sagamihara, Kanagawa 228-8555, Japan³

Received 25 February 2005/ Returned for modification 15 April 2005/ Accepted 8 October 2005

Epiplakin (EPPK) was originally identified as a human epidermal autoantigen. To identify the function of epiplakin, we generated epiplakin "knockout" mice. These mice developed normally, with apparently normal epidermis and hair. Electron microscopy after immunostaining revealed the presence of EPPK adjacent to keratin filaments in wild-type mice, suggesting that epiplakin might associate with keratin. The appearance and localization of keratin bundles in intact epidermal keratinocytes of EPPK^–/– mice were similar to those in wild-type mice. Wounds on the backs of EPPK^–/– mice closed more rapidly than those on the backs of wild-type and heterozygous mice. The outgrowth of keratinocytes from skin explants from knockout mice was enhanced compared to outgrowth from explants from wild-type mice, even in the presence of mitomycin C, suggesting that the difference in keratinocyte outgrowth might be due to a difference in the speed of migration of keratinocytes. At wound edges in wild-type mice, EPPK was expressed in proliferating keratinocytes in conjunction with keratin 6. In EPPK^–/– mice, no similar proliferating keratinocytes were observed, but migrating keratinocytes weakly expressed keratin 6. EPPK was coexpressed with keratin 6 in some keratinocytes in explant cultures from wild mice. We propose that EPPK might be linked functionally with keratin 6.

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* Corresponding author. Mailing address: Department of Anatomy, Biology and Medicine (Dermatology), Oita University, Idaigaoka 1-1, Hasama-machi, Yufu 879-5593, Japan. Phone: 81-97-586-5882. Fax: 81-97-586-5889. E-mail: fujiwara{at}med.oita-u.ac.jp.

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Molecular and Cellular Biology, January 2006, p. 548-558, Vol. 26, No. 2
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.2.548-558.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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