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Development and progression of psoriasiform dermatitis and systemic lesions in the flaky skin (fsn) mouse mutant
J P Sundberg1, M France, D Boggess
1Jackson Laboratory, Bar Harbor, Me. 04609-1500, USA. jps@jax.org
Abstract:
Flaky skin (fsn) mutant mice were originally described as a mouse model for psoriasis accompanied by hematological abnormalities. However, homozygous (fsn/fsn) mice develop a number of other pathological changes. Systematic evaluation of over 300 fsn/fsn and normal littermate control (+/+ or +/fsn) mice was carried out to characterize these changes. Psoriasiform skin lesions were first evident as focal epidermal hyperplasia and inflammation at 2 weeks of age. These lesions became confluent and diffuse by 3-4 weeks of age and were associated with marked dermal infiltration of lymphocytes and small numbers of neutrophils and macrophages. Mast cell numbers increased significantly in the dermis from 2 weeks of age onward. Diffuse dermal neovascularization accompanied these cutaneous changes. Systemic lesions included progressive and massive papillomatosis of the stratified squamous epithelium of the forestomach, hyperplasia and dysplasia of the glandular stomach, increased apoptosis of cecal enterocytes, renal glomerulopathy associated with immune complex and complement deposition, testicular degeneration, mixed inflammatory cell infiltrates and fibrosis around portal triads in the liver, splenomegaly due to massive erythropoiesis, and granulomatous lymphadenitis. This spontaneous mouse mutation provides a useful model for modulating neovascularization and keratinocyte hyperproliferation, especially since the cutaneous changes resemble some forms of psoriasis in humans.
Insights
The flaky skin (fsn) mouse model exhibits psoriasis-like skin lesions and significant systemic pathologies. This mutation offers a valuable tool for studying neovascularization and keratinocyte hyperproliferation.
Area of Science:
- Genetics and Molecular Biology
- Dermatology
- Pathology
Background:
- The flaky skin (fsn) mutant mouse was initially identified as a model for psoriasis and associated hematological abnormalities.
- Homozygous (fsn/fsn) mice present a broader spectrum of pathological changes beyond skin manifestations.
Purpose of the Study:
- To systematically characterize the diverse pathological changes in homozygous (fsn/fsn) mice.
- To evaluate the utility of the fsn/fsn mouse as a model for neovascularization and keratinocyte hyperproliferation.
Main Methods:
- Comprehensive evaluation of over 300 fsn/fsn mice and normal littermate controls.
- Histopathological analysis of skin, forestomach, glandular stomach, cecum, kidneys, testes, liver, and spleen.
Main Results:
- Early onset (2 weeks) of psoriasiform skin lesions with epidermal hyperplasia, inflammation, and dermal infiltration.
- Significant mast cell increase, neovascularization, and systemic lesions including forestomach papillomatosis, gastric hyperplasia, enterocyte apoptosis, glomerulopathy, testicular degeneration, liver fibrosis, splenomegaly with erythropoiesis, and lymphadenitis.
- Cutaneous changes mimic human psoriasis, highlighting the model's relevance.
Conclusions:
- The fsn/fsn mouse mutation induces a wide array of pathological changes, extending beyond its initial description.
- This mouse model is a valuable resource for investigating mechanisms of neovascularization and keratinocyte hyperproliferation, with implications for psoriasis research.