EXPERIMENTAL MODELS

Contributor Information
- Name Manuela Baccarini
- Institute University of Vienna
Tool Details
- Tool name: Krt5-Cre;Braff/f;Raf1f/f Mouse
- Alternate names: RAF, CRAF, BRAF1, RAFB1, B-Raf, RAF/MEK/ERK signalling pathway, Cre-loxP recombination, Eczema
- Tool type: Experimental models
- Tool sub-type: Mouse
- Disease: Atopic Dermatitis
- Model: Transgenic
- Conditional: Yes
- Conditional description: Tissue-specific Cre expression driven by the human Keratin 5 promoter ablating both Braf and Raf1 alleles in the epidermis
- Genetic background and cross history: Krt5-Cre;Braff/f;Raf1f/f mice were generated by crossing Krt5-Cre;Braff/f with Krt5-Cre;Raf1f/f animals
- Zygosity: Homozygous for both floxed Braf and floxed Raf1 alleles
- Description: The skin is the largest organ of the body protecting it from damage and hosting immune system cells. To function effectively as a barrier, the skin continually regenerates producing new cells to replace the old. If the regeneration process fails the skin may produce tumours, and disruption to the immune barrier can lead to autoimmune or allergic skin diseases such as psoriasis or atopic dermatitis. This mouse model has epidermis-specific Braf/Raf1 ablation, mediated by Cre expression in the basal epidermal layer and follicular keratinocytes using the Keratin 5 promoter. In normal conditions Braf and RAF1 operate independently to balance MAPK signalling. Removal of Braf and Raf1 in this model caused mice to develop an allergic disease similar to human atopic dermatitis, characterized by IgE responses (chemokines and Th2-type cytokines) with local and systemic inflammation.
- Research area: Developmental Biology ; Drug Discovery & Development ; Genetic studies
- Production details: Krt5-Cre;Braff/f;Raf1f/f mice were generated by crossing Krt5-Cre;Braff/f with Krt5-Cre;Raf1f/f animals
- For Research Use Only
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References
- • Raguz et al. 2016. Elife. 5:. PMID: 27431613.
- • Epidermal RAF prevents allergic skin disease.
- • Kern et al. 2013. Oncogene. 32(19):2483-92. PMID: 22733131.
- • Essential, non-redundant roles of B-Raf and Raf-1 in Ras-driven skin tumorigenesis.
- • Ehrenreiter et al. 2005. J Cell Biol. 168(6):955-64. PMID: 15753127.
- • Raf-1 regulates Rho signaling and cell migration.