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Krt5-Cre;Braff/f;Raf1f/f Mouse

Invented by Prof Manuela Baccarini from University of Vienna
Invented at University of Vienna
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<p><b>Compound deletion of BRAF and RAF1 in the epidermis leads to severe skin inflammation in adult mice.</b></p> (A) BRAF and RAF1 are efficiently deleted in epidermal cells as shown by PCR analysis of tail tissue and immunoblotting of epidermal lysates isolated from 3 weeks old F/F2 and Δ/Δep2 (n = 4). ACTB is shown as a loading control. (B) Macroscopic appearance of newborn and adult F/F2 and Δ/Δep2 mice. Arrowhead highlights the open eye phenotype of Δ/Δep2 pups. (C) Hematoxylin/eosin (H and E) staining shows epidermal thickening and dermal inflammatory infiltrates in Δ/Δep2 mice. BrdU incorporation confirms hyperproliferation in the basal layer of Δ/Δep2 epidermis. The numbers in the inset represent BrdU+ cells/mm2 of epidermis (n = 5–7, mean ± SEM). Infiltrating cells: activated mast cells (β1 Tryptase+), granulocytes (esterase+), dendritic cells (CD11c+). (D) Quantification of the infiltrating cells: T cells (CD4+ and CD8+), macrophages (F4/80+), total mast cells (MC, toluidine blue+), granulocytes (GR, esterase+). (E) Increased expression of K6, ICAM1, and MHC II in Δ/Δep2 keratinocytes/epidermis. Representative images (C, E) and quantification (D) of 5–7 individual couples. Scale bars, 50 µm. (F) Inflammatory chemokines and cytokines in epidermal lysates (n = 3–4). TSLP levels were determined by immunoblotting and quantified by Image J. ACTB served as a loading control. The results were normalized by arbitrarily setting one of the F/F2 samples as 1 and plotted as mean ± SEM. Data represent mean ± SEM. p = 0.011, p1 = 0.001, p2 = 0.007, p3 = 0.001, p4 = 3.06E-6, p5 = 1.37E-4, p6 = 0.002, p7 = 0.049, p8 = 0.042, p9 = 0.046 and p10 = 0.001.</p></P>
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Image thumbnail for Krt5-Cre;Braf<sup>f/f</sup>;Raf1<sup>f/f</sup> Mouse
Catalogue Number 152988
Antigen/Gene or Protein Targets Epidermis-specific double knockout of Braf and Raf1 alleles
Disease Keywords Atopic Dermatitis
Synonyms RAF, CRAF, BRAF1, RAFB1, B-Raf, RAF/MEK/ERK signalling pathway, Cre-loxP recombination, Eczema
Model Transgenic
Relevance 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.
Production Details Krt5-Cre;Braff/f;Raf1f/f mice were generated by crossing Krt5-Cre;Braff/f with Krt5-Cre;Raf1f/f animals
Conditional Yes
Conditional Description Tissue-specific Cre expression driven by the human Keratin 5 promoter ablating both Braf and Raf1 alleles in the epidermis
Mouse Genetic Background/Cross History Mouse strain: 129S1/SvImJ also known as 129S1
Zygosity Homozygous for both floxed Braf and floxed Raf1 alleles
Research Area Bacteriology, Developmental Biology, Drug Discovery & Development, Genetic Studies Tools

References

There are 6 reference entries for this reagent.

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References: 6 entries

Raguz et al. 2016. Elife. 5:. PMID: 27431613.

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Epidermal RAF prevents allergic skin disease.

Europe PMC ID: 27431613

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Kern et al. 2013. Oncogene. 32(19):2483-92. PMID: 22733131.

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Essential, non-redundant roles of B-Raf and Raf-1 in Ras-driven skin tumorigenesis.

Europe PMC ID: 22733131

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Ehrenreiter et al. 2005. J Cell Biol. 168(6):955-64. PMID: 15753127.

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Raf-1 regulates Rho signaling and cell migration.

Europe PMC ID: 15753127

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References: 6 entries

Raguz et al. 2016. Elife. 5:. PMID: 27431613.

View  

Epidermal RAF prevents allergic skin disease.

View  

Kern et al. 2013. Oncogene. 32(19):2483-92. PMID: 22733131.

View  

Essential, non-redundant roles of B-Raf and Raf-1 in Ras-driven skin tumorigenesis.

View  

Ehrenreiter et al. 2005. J Cell Biol. 168(6):955-64. PMID: 15753127.

View  

Raf-1 regulates Rho signaling and cell migration.

View  

Add a reference

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