IL-23 Induced Psoriasis (Mouse)

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Induction:

Beginning on study day 0, and continuing every other day until study day 20, mice will be anesthetized with Isoflurane and have 20^1 of PBS with 0.5|ig of recombinant mouse lL-23 injected in the pinna of the right ear.

Disease Parameters/Progression:

It is assumed that this model causes only minimal to mild pain in one of the rodent’s ears. Redness, some inflammation, hyperplasia and scabbing may occur for the duration of the 21 day study. Animals will be monitored daily, however it is highly unlikely that the disease will be severe enough to trigger euthanasia. Any animals displaying signs of distress will enrolled in the Health Monitoring Program and the Health Assessment scoring system will determine euthanasia.

Dosing Paradigms:

Route of administration: SC, PO, IP, IV

Clinical Assessment:

On study days 0 (baseline) 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21 the thickness of the both ears will be measured using a mechanical caliper. The left ear will be used as an animal control.

Notes:

Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders in adults, affecting ~2% of Caucasian individuals’. While an underlying genetic component to the disease has been acknowledged for many years’”^, important aspects of the complex autoimmune inflammatory mechanisms involved in the pathogenesis of psoriasis are still poorly understood. It is our hope that this model will allow us to help customers identify novel treatments for this condition.

Optional Endpoint

PK/PD blood collections
Cytokine/chemokine analysis via Luminex(R)
Other sandwich ELISAs
CBC/clinical chemistry analysis
Soft tissue collection
Histopathologic analysis
Immunohistochemistry analysis

References

Krueger JG, The immunologic basis for the treatment of psoriasis with new biologic agents J Am Acad Dermatol. 2002 Jan;46(l):l-23; quiz 23-6.
Schon, M.P, Animal Models of Psoriasis – what can we learn from them?, Invest Dermatol, 1 9 9 9 11 2 : 4 0 5 – 4 1 0
Lowes, M.A., Bowcock, A.M., and Krueger, J.G. 2007. Pathogenesis and therapy of psoriasis. 445:866-873.
Wolfram JA, Diaconu D, Hatala DA, Rastegar J, Knutsen DA, Lowther A, Askew D, Gilliam AC, McCormick TS, Ward NL. Keratinocyte but not endothelial cell specific overexpression of Tie-2 leads to the development of psoriasis. Am J Pathol, 2009; 174: 1443- 1458
Schon, M.P., and Boehncke, W.H. 2005. Psoriasis. N. Engl. J. Med. 352:1899-1912.
Bowcock, A.M., and Krueger, J.G. 2005. Getting under the skin: the immunogenetics of psoriasis. Nat. Rev. Immunol. 5:699-711.

General Inflammation