Mouse Models of Atopic Eczema Critically Evaluated

Gutermuth, Jan; Ollert, Markus; Ring, Johannes; Behrendt, Heidrun; Jakob, Thilo

doi:10.1159/000082099

Cited by 39 publications

(38 citation statements)

References 134 publications

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“…In case of developing in vivo animal model of human disease of atopic dermatitis, we must consider the following points like a) Model organism displays the main clinical symptoms of the disease; b) Induction of the disease phenotype is reproducible; c) Possible transfer of data to man (Gutermuth et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

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Mouse model of DNCB-induced atopic dermatitis

Hamad

Han

Rather

2017

Bangladesh J Pharmacol

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Atopic dermatitis is a skin disease characterized by allergic skin inflammation, redness and itching. The animal model is necessary to find out new drugs. The DNCB-induced animal model of atopic dermatitis includes the following steps: 1) Selection of animals; 2) Shaving of dorsal skin; 3) Applying DNCB once in 24 hours for three days; 4) Monitoring the development of atopy on day 4 post DNCB application. Further, the efficacy of reference drug can be determined by applying on the atopy skin, depends on the nature and aim of the work.

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Section: Discussionmentioning

confidence: 99%

“…); h) Environmental factors (housing, feeding, day-night rhythm, climate, stress, etc.) (Gutermuth et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Mouse model of DNCB-induced atopic dermatitis

Hamad

Han

Rather

2017

Bangladesh J Pharmacol

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“…43) remains also to be examined. Transgenic mice overexpressing TSLP in different tissues, as well as tissue-selective conditional somatic mutations of the TSLP gene, should offer new useful models (44,45) for investigating further the pathogenesis of atopic diseases and testing possible therapies.…”

Section: ) Increasesmentioning

confidence: 99%

Retinoid X receptor ablation in adult mouse keratinocytes generates an atopic dermatitis triggered by thymic stromal lymphopoietin

Messaddeq

Teletin

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

203

206

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To investigate the role of retinoid X receptors (RXRs) in epidermal homeostasis, we generated RXR␣␤ ep؊/؊ somatic mutants in which both RXR␣ and RXR␤ are selectively ablated in epidermal keratinocytes of adult mice. These mice develop a chronic dermatitis mimicking that observed in atopic dermatitis (AD) patients. In addition, they exhibit immunological abnormalities including elevated serum levels of IgE and IgG, associated with blood and tissue eosinophilia, indicating that keratinocyte-selective ablation of RXRs also generates a systemic syndrome similar to that found in AD patients. Furthermore, the profile of increased expression of cytokines and chemokines in skin of keratinocyte-selective RXR␣␤-ablated mutants was typical of a T helper 2-type inflammation, known to be crucially involved in human AD pathogenesis. Finally, we demonstrate that thymic stromal lymphopoietin, whose expression is rapidly and strongly induced in RXR␣␤-ablated keratinocytes, plays a key role in initiating the skin and systemic AD-like pathologies.keratinocyte-selective gene ablation ͉ nuclear receptors ͉ conditional mutagenesis ͉ Cre-ER T2 A topic dermatitis (AD), a chronic skin inflammatory disease with a strong genetic component that affects children (10-20%) and adults (1-3%), is characterized by pruritic and eczematoid skin lesions, associated with systemic immunological abnormalities, including peripheral eosinophilia and hyper IgE immunoglobulinemia (1). Immunological mechanisms have been involved in AD pathogenesis (2), but the possible role of epidermal keratinocytes in AD initiation and maintenance is still largely unexplored (3).Nuclear receptors (NRs) belong to a superfamily of transcriptional regulators that include ligand-dependent and orphan receptors (4, 5). NRs play critical roles as signal transducers in vertebrate development and homeostasis, including immune functions (4, 6-8). Within the NR superfamily, the retinoid X receptor isotypes (RXR ␣, ␤, and ␥) play a key role as heterodimeric partners for some 15 NRs, e.g., retinoic acid receptors, 1,25-dihydroxyvitamin D 3 receptor (VDR), peroxisome proliferator-activated receptors, and liver X activated receptors (4, 5, 9). Ligand-dependent transcriptional activation by NRs requires the integrity of the core of activation function 2 (AF-2) (the ␣-helix 12 of the ligand-binding domain; see refs. 9 and 10).In epidermis, RXR␣ is predominant, RXR␤ level is lower, and RXR␥ is undetectable (11-13). Keratinocyte-selective ablation of RXR␣ in adult mouse skin results in a number of abnormalities, including a progressive alopecia, keratinocyte hyperproliferation, and abnormal differentiation, and an inflammatory reaction (11,14). In contrast, the skin of RXR␤-null mice is apparently normal (11,14,15).To investigate the origin of this inflammatory reaction and to avoid any functional redundancies between keratinocytic RXR␣ and RXR␤, we have now generated RXR␣␤ epϪ/Ϫ somatic mutants in which both RXR␣ and RXR␤ are selectively ablated in epidermal keratinocytes of adult mice. T...

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“…Surprisingly, treated mice displayed an increased eczema severity and IgE levels, suggesting a downmodulatory role for IL-4 and IL-13 in the skin inflammatory immune response [for a review, see ref. [17]. This raised the possibility that IL-4 and IL-13 may regulate the production of proinflammatory cytokines by monocytes/macrophages in AE etiology, as well as in autoimmune diseases [18].…”

Section: Differentially Expressed Genes In Monocytes and Eosinophilsmentioning

confidence: 99%

“…Additionally, another regulatory cytokine, the IL-10Rα gene, was found among a candidate locus of these mice by reciprocally crossing and subsequently backcrossing NC/Nga with BALB/c mice [for a review, see ref. [17]. Indeed, patients with IPEX syndrome lacking the FOXP3 gene responsible for regulatory T cells exert systemic skin eczema and hyper IgE as well [40].…”

Section: Genetic Analysis Of Ae-susceptible Genesmentioning

confidence: 99%

Much Atopy about the Skin: Genome-Wide Molecular Analysis of Atopic Eczema

Saito

2005

Int Arch Allergy Immunol

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Background: Atopic eczema (AE) is a chronic inflammatory skin disorder with an increasing prevalence in industrialized countries. Methods: Genox Research Incorporation was founded in 1996 to identify new genes involved in allergic diseases in collaboration with the National Children’s Hospital in Tokyo. In the AE project, they have discovered several hundred new genes and partial DNA sequences by mainly using microarrays. Here, I review the results obtained using transcriptome analysis, performed by Genox and other investigators. Results:Transcriptome analysis using skin lesion, CD4+ T cells, monocytes and eosinophils derived from AE patients identified some differentially expressed genes which became biologically relevant in the following studies. Missing linkages between these genes have been found due to the recent development of genomics. Conclusion:Many AE-related genes found in the genome-wide studies still remain to be determined regarding their functions and to be systemically organized. After the comprehensive characterization of these genes by further studies, we will identify the precise molecular mechanisms involved in AE and other diseases.

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Mouse Models of Atopic Eczema Critically Evaluated

Cited by 39 publications

References 134 publications

Mouse model of DNCB-induced atopic dermatitis

Mouse model of DNCB-induced atopic dermatitis

Retinoid X receptor ablation in adult mouse keratinocytes generates an atopic dermatitis triggered by thymic stromal lymphopoietin

Much Atopy about the Skin: Genome-Wide Molecular Analysis of Atopic Eczema

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