1. ^*Department of Social and Environmental Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
2. ^†Department of Dermatology, Kurume University School of Medicine, Fukuoka, Japan
3. ^‡Collaborative Research Center for Advanced Science and Technology, Osaka University, Osaka, Japan

Correspondence: Dr. Junji Takeda, Department of Social and Environmental Medicine (H3), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan Email: takeda@mr-envi.med.osaka-u.ac.jp

Received 16 February 2004; Revised 27 April 2004; Accepted 27 May 2004; Published online 10 September 2004.

Abstract

Desmoyokin was first isolated from bovine muzzle epidermis and thought to be an epidermal desmosome-related protein. We previously demonstrated that the Desmoyokin gene is identical to the Ahnak gene, which is expressed ubiquitously and downregulated in neuroblastomas. It was assumed Ahnak/Desmoyokin was associated with epidermal cell adhesion, tumorigenesis, cell proliferation and differentiation, and embryonic development. To determine the precise biological function of Ahnak/Desmoyokin, we generated a null mutation in ES cells and mice. The resultant Ahnak/Desmoyokin-deficient ES cells normally differentiated into embryoid bodies and neural cells. The mutant mice were viable and fertile and showed no gross developmental defects. Electron microscopic examination of skin sections demonstrated that the ultrastructure of epidermal intercellular junctions, including desmosomes, of the mutant mice was indistinguishable from that of wild-type mice. Two-stage chemical skin carcinogenesis experiments showed no difference in frequency or onset of cutaneous tumor formation between wild-type and mutant mice. Moreover, no tumorigenesis was observed in other tissues and organs of mutant mice up to 2 y of age. These results lead us to conclude that Ahnak/Desmoyokin deficiency has only a minimal effect on epidermal cell adhesion, tumorigenesis, cell proliferation and differentiation, and overall mouse development.