OVEREXPRESSION OF BONE MORPHOGENETIC PROTEIN-6 (BMP-6) IN THE EPIDERMIS OF TRANSGENIC MICE - INHIBITION OR STIMULATION OF PROLIFERATION DEPENDING ON THE PATTERN OF TRANSGENE EXPRESSION AND FORMATION OF PSORIATIC LESIONS

Bone morphogenetic protein-6 (BMP-6) belongs to the family of TGF-beta -related growth factors. In the developing epidermis, expression of BM P-6 coincides with the onset of stratification. Expression persists pe rinatally but declines after day 6 postpartum, although it can still b e detected in adult skin by reverse transcriptase-polymerase chain rea ction (RT-PCR) analysis. We constitutively overexpressed BMP-6 in supr abasal layers of interfollicular epidermis in transgenic mice using a keratin 10 promoter. All mice expressing the transgene developed abnor malities in the skin, indicating an active transgene-derived factor. D epending on the pattern of transgene expression, the effects on prolif eration and differentiation were completely opposite. Strong and unifo rm expression of the BMP-6 transgene resulted in severe repression of cell proliferation in embryonic and perinatal epidermis but had margin al effects on differentiation. Weaker and patchy expression of the tra nsgene evoked strong hyperproliferation and parakeratosis in adult epi dermis and severe perturbations of the usual pattern of differentiatio n. These perturbations included changes in the expression of keratins and integrins. Together with an inflammatory infiltrate both in the de rmis and in the epidermis, these aspects present all typical histologi cal and biochemical hallmarks of a human skin disease: psoriasis.