Keratinocyte-specific deletion of SHARPIN induces atopic dermatitis-like inflammation in mice. 2020

John P Sundberg, and C Herbert Pratt, and Leslie P Goodwin, and Kathleen A Silva, and Victoria E Kennedy, and Christopher S Potter, and Anisa Dunham, and Beth A Sundberg, and Harm HogenEsch
The Jackson Laboratory, Bar Harbor, ME, United States of America.

Spontaneous mutations in the SHANK-associated RH domain interacting protein (Sharpin) resulted in a severe autoinflammatory type of chronic proliferative dermatitis, inflammation in other organs, and lymphoid organ defects. To determine whether cell-type restricted loss of Sharpin causes similar lesions, a conditional null mutant was created. Ubiquitously expressing cre-recombinase recapitulated the phenotype seen in spontaneous mutant mice. Limiting expression to keratinocytes (using a Krt14-cre) induced a chronic eosinophilic dermatitis, but no inflammation in other organs or lymphoid organ defects. The dermatitis was associated with a markedly increased concentration of serum IgE and IL18. Crosses with S100a4-cre resulted in milder skin lesions and moderate to severe arthritis. This conditional null mutant will enable more detailed studies on the role of SHARPIN in regulating NFkB and inflammation, while the Krt14-Sharpin-/- provides a new model to study atopic dermatitis.

UI MeSH Term Description Entries
D007073 Immunoglobulin E An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE). IgE
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D003876 Dermatitis, Atopic A chronic inflammatory genetically determined disease of the skin marked by increased ability to form reagin (IgE), with increased susceptibility to allergic rhinitis and asthma, and hereditary disposition to a lowered threshold for pruritus. It is manifested by lichenification, excoriation, and crusting, mainly on the flexural surfaces of the elbow and knee. In infants it is known as infantile eczema. Eczema, Atopic,Eczema, Infantile,Neurodermatitis, Atopic,Neurodermatitis, Disseminated,Atopic Dermatitis,Atopic Eczema,Atopic Neurodermatitis,Disseminated Neurodermatitis,Infantile Eczema
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071999 S100 Calcium-Binding Protein A4 An S100 protein characterized by four helix bundles that form N- and C-terminal EF HAND MOTIFS. It functions as a homodimer and interacts with both intracellular and extracellular signaling proteins. Aberrant S100A4 activity is associated with NEOPLASM METASTASIS; FIBROSIS; and RHEUMATOID ARTHRITIS. Calvasculin Protein,Fibroblast-Specific Protein 1,Metastasin Protein,Placental Calcium-Binding Protein,S100A4 Protein,Calcium-Binding Protein, Placental,Fibroblast Specific Protein 1,Placental Calcium Binding Protein,S100 Calcium Binding Protein A4
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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