| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Dermatology and Allergic Diseases, and
Institute of Orthopaedic Research and Biomechanics, University of Ulm, Ulm, Germany;
Department of Dermatology and Center for Molecular Medicine, University of Cologne, Cologne, Germany;
Department for Cell and Molecular Biology, Section for Medical Inflammation Research, University of Lund, Lund, Sweden; and
¶ Department of Biostatistics, Johns Hopkins University, Baltimore, MD 21205
Psoriasis is a frequently occurring inflammatory skin disease characterized by thickened erythematous skin that is covered with silvery scales. It is a complex genetic disease with both heritable and environmental factors contributing to onset and severity. The CD18 hypomorphic PL/J mouse reveals reduced expression of the common chain of 
2 integrins (CD11/CD18) and spontaneously develops a skin disease that closely resembles human psoriasis. In contrast, CD18 hypomorphic C57BL/6J mice do not demonstrate this phenotype. In this study, we have performed a genome-wide scan to identify loci involved in psoriasiform dermatitis under the condition of low CD18 expression. Backcross analysis of a segregating cross between susceptible CD18 hypomorphic PL/J mice and the resistant CD18 hypomorphic C57BL/6J strain was performed. A genome-wide linkage analysis of 94 phenotypically extreme mice of the backcross was undertaken. Thereafter, a complementary analysis of the regions of interest from the genome-wide screen was done using higher marker density and further mice. We found two loci on chromosome 10 that were significantly linked to the disease and interacted in an additive fashion in its development. In addition, a locus on chromosome 6 that promoted earlier onset of the disease was identified in the most severely affected mice. For the first time, we have identified genetic regions associated with psoriasis in a mouse model resembling human psoriasis. The identification of gene regions associated with psoriasis in this mouse model might contribute to the understanding of genetic causes of psoriasis in patients and pathological mechanisms involved in development of disease.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants to K.S.-K. and T.K. from the Center for Molecular Medicine, University of Cologne (TV60, BMBF 01 KS 9502), the individual research grant from the German Research Foundation (Deutsche Forschungsgemeinschaft) (SCHA 411/12-1, 12-2), the Swedish Strategic Foundation, and the Swedish Science Research Council. This research was further supported through a European Community Marie Curie Fellowship "Stay at Training Site" in 2000 between the University of Lund and the Commission of the European Communities.
2 D.K. and A.-K.B.L. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Karin Scharffetter-Kochanek, Department of Dermatology and Allergic Diseases, University of Ulm, Maienweg 12, D-89081 Ulm, Germany. E-mail address: karin.scharffetter-kochanek{at}uniklinik-ulm.de
4 Abbreviations used in this paper: PSORS, psoriasis susceptibility; PASI, psoriasis area and severity index; QTL, quantitative trait locus; LOD, logarithm of odds; CD18hypo, CD18 hypomorphic; LODint, LOD support interval; CM, centimorgan; Mb, megabase; AUC, area under the curve.
This article has been cited by other articles:
|
|
 |
|
  H. Wang, D. Kess, A.-K. B. Lindqvist, T. Peters, A. Sindrilaru, M. Wlaschek, R. Blakytny, R. Holmdahl, and K. Scharffetter-Kochanek A 9-Centimorgan Interval of Chromosome 10 Controls the T Cell-Dependent Psoriasiform Skin Disease and Arthritis in a Murine Psoriasis Model J. Immunol., April 15, 2008; 180(8): 5520 - 5529. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
