Scientists at the Research Institute of Molecular Pathology in Vienna have developed the first true animal model for psoriasis and have been able to address the initial steps and possible causes of the disease. The science journal NATURE publishes a coverstory in its September 15 issue.
Psoriasis is a chronic disease of unsolved pathogenesis affecting between one and three percent of the general population. It is characterized by inflamed, scaly and frequently disfiguring skin lesions and often accompanied by arthritis of the small joints of the hands and feet.
The underlying causes of psoriasis are as yet unknown. It has been widely regarded as an auto-immune disease that affects the skin and the joints. Alternatively, it was characterized as a skin disorder with immunological consequences. Up to now, it was hard to get a clearer picture, mostly because the disase could not be reproduced and studied in animals.
Scientists at the Research Institute of Molecular Pathology (IMP), the basic research center of Boehringer Ingelheim in Vienna (Austria), have now been able to solve some of the puzzling aspects of the mystery. A team led by Senior Scientist Erwin F. Wagner was able to design a particularly useful strain of mice. The animals carry the disposition for psoriasis which can be activated on purpose at any time by a "genetic switch". Within two weeks following the trigger, the adult mice develop the hallmarks of psoriasis. Whereas previous models were only able to reproduce the skin lesions, the new strain also develops psoriatic arthritis. Due to the close resemblance of the clinical and histological picture of human psoriasis, the new disease-model is ideally suited to study in detail all aspects of pathogenesis.
The science journal NATURE publishes the research results in today's issue (September 15, 2005). The magazine also devotes the cover to the psoriasis-mice, hoping that they will solve the mystery about the cause of the disease. Author Rainer Zenz from the IMP is optimistic. "We strongly believe that this model will be highly suitable for future pre-clinical studies ultimately aimed at understanding and curing this widespread disease."
The work at the IMP was carried out in collaboration with researchers from the German Cancer Research Center in Heidelberg and with clinicians from the Medical University of Vienna. The first clues as to the genetic basis of psoriasis came from skin biopsies from the Department of Dermatology at Vienna's University hospital. In lesional skin of severe psoriasis, the IMP-scientists found greatly reduced activity of the JunB-gene. Human JunB belongs to a family of transcription factors and is known to regulate cell proliferation, differentiation and stress responses. However, mice lacking JunB do not show any signs of psoriasis. It is the combined deletion of JunB and c-Jun, a closely related gene, that brings forth the typical symptoms of the disease in mice. The disease-prone animals which were generated at the IMP carry a double mutation which can be induced by tamoxifen.
Further studies on the mutant mice already prove the model to be very powerful. Recent experiments could even shake some long-held beliefs: The IMP-researchers found that they could induce psoriasis even in mice lacking B- and T-cells, that is without a functioning immune system. This result contradicts the picture of an autoimmune disease mediated by T-cells as the initial event leading to the diesease. Instead, current data support the hypothesis that epidermal alterations are sufficient to initiate both skin lesions and arthritis in psoriasis. Or, as Nature puts it, "outside-in" rather than "inside-out".
The work was also supported by grants from the Austrian Science Fund FWF.
IMP
The IMP is a basic research institute in Vienna, Austria. Its main sponsor is Boehringer Ingelheim International, headquartered in Germany. With over 200 employees from 28 different nations, the IMP is a Center of Excellence in the life sciences and the core unit of the Campus Vienna Biocenter. Research at the IMP aims at elucidating the molecular basis of normal development and disease.
Contact:
Dr. Heidemarie Hurtl
IMP Communications
Tel.: 43-179-730-358
hurtl@imp.univie.ac.at
Prof. Erwin Wagner
wagner@imp.univie.ac.at
Journal
Nature