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Identification of susceptibility loci for skin disease in a murine psoriasis model

Kess, Daniel ; Lindqvist, Anna-Karin LU ; Peters, Thorsten ; Wang, Honglin ; Zamek, Jan ; Nischt, Roswitha ; Broman, Karl W. ; Blakytny, Robert ; Krieg, Thomas and Holmdahl, Rikard LU , et al. (2006) In Journal of Immunology 177(7). p.4612-4619
Abstract
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 beta(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... (More)
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 beta(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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
177
issue
7
pages
4612 - 4619
publisher
American Association of Immunologists
external identifiers
  • wos:000240787400048
  • pmid:16982899
  • scopus:33749155652
ISSN
1550-6606
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019)
id
bb24e7a0-732b-41ef-8f9a-aef4be1d7198 (old id 392678)
alternative location
http://www.jimmunol.org/cgi/content/abstract/177/7/4612
date added to LUP
2016-04-01 16:26:30
date last changed
2020-01-29 05:55:33
@article{bb24e7a0-732b-41ef-8f9a-aef4be1d7198,
  abstract     = {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 beta(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.},
  author       = {Kess, Daniel and Lindqvist, Anna-Karin and Peters, Thorsten and Wang, Honglin and Zamek, Jan and Nischt, Roswitha and Broman, Karl W. and Blakytny, Robert and Krieg, Thomas and Holmdahl, Rikard and Scharffetter-Kochanek, Karin},
  issn         = {1550-6606},
  language     = {eng},
  number       = {7},
  pages        = {4612--4619},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Identification of susceptibility loci for skin disease in a murine psoriasis model},
  url          = {http://www.jimmunol.org/cgi/content/abstract/177/7/4612},
  volume       = {177},
  year         = {2006},
}