EXPERIMENTAL MODELS

Contributor Information
- Name Fiona Watt
- Institute Cancer Research UK, London Research Institute: Lincoln's Inn Fields
Tool Details
- Tool name: Inva5b1 Mouse
- Tool type: Experimental models
- Tool sub-type: Mouse
- Disease: Psoriasis
- Conditional: Yes
- Conditional description: Conditional transgenic
- Genetic background and cross history: Involucrin-integrin transgene expression constructs were injected into fertilised oocytes from F1 hybrid CBA/C57BL/6 mice. Transgene-positive mice were back-crossed to generate individual founder lines. The a5 transgene founder line was mated to the b1 integrin founder line to generate mice expressing both a5 and b1 integrin transgenes.
- Phenotype: The Inv-a5b1 mouse presents a phenotype very similar to psoriasis, and is an ideal tool for study of the disease in vivo. Abnormal keratinocyte differentiation - widespread thickening of the epidermis Keratinocyte hyperproliferation - flaking epidermis. High numbers of Ki-67 positive cells in all basal and suprabasal layers - Keratin 6 expression in all epidermal layers - Inflammatory skin lesions - dilated capillaries and reddening of skin - Pustules with neutrophil infiltration within or beneath cornified layers - high numbers of CD4 and CD8 lymphocytes within epidermis There are a number of other psoriasis disease models please see the related page.
- Description: Disease model for psoriasis; in vivo study of human a5 and b1 integrin transgene expression in skin A transgenic mouse expressing integrin a5B1 in the suprabasal layers of the epidermis. The mouse exhibits many of the characteristics associated with psoriasis including hyperproliferation of keratinocytes and infiltration of lymphocytes. Granted patents are associated with this mouse (US6187993 and AU0698317). Alpha5beta1 integrin transgenes under involucrin promoter, giving conditional suprabasal epidermal expression. Psoriasis phenotype
- Research area: Cell biology; Genetics
- Production details: Involucrin-integrin transgene expression constructs were injected into fertilised oocytes from F1 hybrid CBA/C57BL/6 mice. Transgene-positive mice were back-crossed to generate individual founder lines. The a5 transgene founder line was mated to the b1 integrin founder line to generate mice expressing both a5 and b1 integrin transgenes.
- Additional notes: The Inv-a5b1 mouse presents a phenotype very similar to psoriasis, and is an ideal tool for study of the disease in vivo. Abnormal keratinocyte differentiation - widespread thickening of the epidermis Keratinocyte hyperproliferation - flaking epidermis. High numbers of Ki-67 positive cells in all basal and suprabasal layers - Keratin 6 expression in all epidermal layers - Inflammatory skin lesions - dilated capillaries and reddening of skin - Pustules with neutrophil infiltration within or beneath cornified layers - high numbers of CD4 and CD8 lymphocytes within epidermis There are a number of other psoriasis disease models please see the related page.
- For Research Use Only
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References
- • Haase et al. 2001. J Clin Invest. 108(4):527-36. PMID: 11518726.
- • A role for mitogen-activated protein kinase activation by integrins in the pathogenesis of psoriasis.
- • Carroll et al. 1995. Cell. 83(6):957-68. PMID: 8521519.
- • Carroll et al. 1995. Cell. 83(6):957-68. PMID: 8521519.
- • Suprabasal integrin expression in the epidermis of transgenic mice results in developmental defects and a phenotype resembling psoriasis.