InvEE mouse

Gene/Protein Targets

MAPK/ERK Kinase 1 (MEK1) constituitively active mutant

Relevance: Disease model for psoriasis; in vivo study of constituitively active murine MEK1 mutant (S217E/S221E) in skin.
Model Type: Conditional, Transgenic Models
Genetic Background: CBA/C57BL/6
Zygosity: Heterozygous
Phenotype Keywords: Skin abnormalities
Disease Keywords: Psoriasis
Production Details:

An involucrin-MEK1 transgene expression construct was injected into male pronucleus of fertilised oocytes from F1 hybrid CBA/C57BL/6 mice. Transgene-positive mice were mated with wildtype F1 CBA/C57BL/6 to generate founder lines.

References:

Hobbs et al. 2004. Journal of Investigative Dermatology. 123:503-15. PMID: 15304090Read more

Notes:

The InvEE mouse presents a phenotype very similar to psoriasis, and is an ideal tool for study of the disease in vivo.

InvEE mice demonstrate key features of human psoriasis:

Abnormal keratinocyte differentiation;

- hyperkeratosis

- widespread thickening of the epidermis

- Keratin10 expression delayed (no parakeratosis observed)

- accumulation of cornified material on footpads, leading to development of horny masses

- development of papillomas at sites of wounding

Keratinocyte hyperproliferation;

- scruffy coats, flaking epidermis

- high numbers of Ki-67 and BrdU positive cells in all basal and suprabasal layers

- Keratin14 staining in suprabasal layer

- Keratin 6 and 7 expression in all epidermal layers

Inflammatory skin lesions;

- high numbers of CD4 (and some CD8) lymphocytes within epidermis

- increased infiltration of macrophage and dendritic cells in the dermis, neutrophil infiltration in the dermis

For more psoriasis disease models, see also Inv-a2b1 mouse; Inv-a3b1 mouse; Inv-a5b1 mouse.