1. ^*Centre for Cutaneous Research, Queen Mary and Westfield College, London, UK
2. ^†Harvard Skin Disease Research Center, Boston, Massachusetts, U.S.A.
3. ^‡Department of Dermatology, University of Vienna Medical School, Vienna, Austria
4. ^§Department of Dermatology, Charité Humboldt-University, Berlin, Germany
5. ^¶Department of Dermatology, University Hospital Eppendorf, University of Hamburg, Germany

Correspondence: Dr Sven Müller-Röver, Centre for Cutaneous Research, Queen Mary and Westfield College, 2 Newark Street, London E1 2AT, UK. Email: mueller-rover@gmx.net

Received 5 January 1999; Revised 21 January 1999.

Abstract

Hair follicle (HF) morphogenesis and cycling are characterized by a tightly controlled balance of proliferation, differentiation and apoptosis. The members of the bcl-2 family of proto-oncogenes are important key players in the apoptosis control machinery of most cell types. Bcl-2, an apoptosis inhibitor, and Bax, an apoptosis promoter, show tightly regulated, hair cycle-dependent expression patterns: during catagen, the distal ORS of the HF remains strongly positive for Bcl-2 and Bax; in contrast, the proximal epithelial part of the HF loses most Bcl-2 expression while it remains strongly positive for Bax. In Bcl-2 null mice, skin becomes markedly hypopigmented during the first postnatal anagen probably due to increased melanocyte apoptosis. Reportedly, these mice also show a retardation of the first anagen development after birth. Transgenic mice overexpressing Bcl-2 under the control of the keratin-1 promoter display multifocal epidermal hyperplasia and aberrant expression of keratin-6, while alterations of HF cycling have not been investigated. Surprisingly, Bcl-2 overexpression under the control of the keratin-14 promoter leads to accelerated catagen progression and increased chemotherapy-induced apoptosis, HF dystrophy and alopecia. Transgenic mice overexpressing Bcl-X(L), another anti-apoptotic bcl-2 family member, under the control of the K14 promoter, reportedly also display accelerated catagen development. These and other Bcl-2 transgenic and null mice are now available to further dissect the as yet unclear, and likely complex, role of Bcl-2 in HF growth and pigmentation.