Canine Models of Atopic Dermatitis: A Useful Tool with Untapped Potential

Marsella, Rosanna; Girolomoni, Giampiero

doi:10.1038/jid.2009.98

Cited by 135 publications

(132 citation statements)

References 42 publications

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“…4 Similarity in the pathogenesis and clinical manifestation between human and canine AD (cAD) has been reported. 5,6 Furthermore, genetic inheritance of AD was also reported in both species. 7 It is important to validate whether skin barrier impairment caused by a FLG gene mutation is associated with cAD, as shown in human AD.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Canine Filaggrin: Gene Structure and Protein Expression in Dog Skin

Kanda¹,

Sasaki²,

Shiohama³

et al. 2013

Advances in Veterinary Dermatology

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Background -Filaggrin (FLG) is a key protein for skin barrier formation and hydration of the stratum corneum. In humans, a strong association between FLG gene mutations and atopic dermatitis has been reported. Although similar pathogenesis and clinical manifestation have been argued in canine atopic dermatitis, our understanding of canine FLG is limited.Hypothesis ⁄ Objectives -The aim of this study was to determine the structure of the canine FLG gene and to raise anti-dog FLG antibodies, which will be useful to detect FLG protein in dog skin.Methods -The structure of the canine FLG gene was determined by analysing the publicly available canine genome DNA sequence. Polyclonal anti-dog FLG antibodies were raised based on the canine FLG sequence analysis and used for defining the FLG expression pattern in dog skin by western blotting and immunohistochemistry.Results -Genomic DNA sequence analysis revealed that canine FLG contained four units of repeated sequences corresponding to FLG monomer protein. Western blots probed with anti-dog FLG monomer detected two bands at 59 and 54 kDa, which were estimated sizes. The results of immunohistochemistry showed that canine FLG was expressed in the stratum granulosum of the epidermis as a granular staining pattern in the cytoplasmic region.Conclusions and clinical importance -This study revealed the unique gene structure of canine FLG that results in production of FLG monomers larger than those of humans or mice. The anti-dog FLG antibodies raised in this study identified FLG in dog skin. These antibodies will enable us to screen FLG-deficient dogs with canine atopic dermatitis or ichthyosis.

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Section: Introductionmentioning

confidence: 99%

Characterization of Canine Filaggrin: Gene Structure and Protein Expression in Dog Skin

Kanda¹,

Sasaki²,

Shiohama³

et al. 2013

Advances in Veterinary Dermatology

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“…Atopic dermatitis (AD) is a chronic inflammatory dermatopathy that is frequently complicated by secondary bacterial infection in both dogs and humans [21]. In human AD patients, it is thought that the inflammatory cytokines in the skin, such as IL-4 and IL-13, reduce the expression of hBD3 [22].…”

Section: Introductionmentioning

confidence: 99%

Activity, Expression and Genetic Variation of Canine β-Defensin 103: A Multifunctional Antimicrobial Peptide in the Skin of Domestic Dogs

Leonard

Marks²,

Outerbridge³

et al. 2012

J Innate Immun

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The skin functions as more than a physical barrier to infection. Epithelial cells of the skin can synthesize antimicrobial peptides, including defensins, which exhibit direct antimicrobial activity. Here we characterize the expression pattern, genetic variation and activity of the major β-defensin expressed in canine skin, canine β-defensin 103 (CBD103). The gene encoding CBD103 exhibits two forms of polymorphism: a common 3-basepair deletion allele and a gene copy-number variation. Golden retrievers and Labrador retrievers were the only breeds that encoded the variant allele of CBD103, termed CBD103ΔG23. Both these breeds also exhibited a CBD103 gene copy-number polymorphism that ranged from 2 to 4 gene-copies per diploid genome. Recombinant CBD103 and CBD103ΔG23, as well as the human ortholog human β-defensin 3 (hBD3) and hBD3ΔG23, showed potent and comparable antimicrobial killing against both methicillin-susceptible and methicillin-resistant Staphylococcus pseudintermedius. Skin biopsy specimens from dogs with atopic dermatitis revealed CBD103 expression levels similar to those in healthy controls and comparable at lesional and nonlesional sites. This expression pattern in dogs differs from the previously reported reduced expression of the human ortholog in atopic dermatitis. Overall, the similarities of CBD103 and its human ortholog reported here support the notion that the domestic dog may serve as a valuable model for studying β-defensin biology in the skin.

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“…Histologically and immunologically the similarity of AD between dogs and people is striking, making dogs the closest naturally occurring animal model to study this disease in people [44]. Atopy patch test reactions in dogs mimic naturally occurring lesions and are very similar to what is reported in human medicine [45].…”

Section: Atopic Dermatitis: Comparative Observationsmentioning

confidence: 53%

Animal Models of Allergic Diseases

Santoro

Marsella

2014

Veterinary Sciences

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Allergic diseases have great impact on the quality of life of both people and domestic animals. They are increasing in prevalence in both animals and humans, possibly due to the changed lifestyle conditions and the decreased exposure to beneficial microorganisms. Dogs, in particular, suffer from environmental skin allergies and develop a clinical presentation which is very similar to the one of children with eczema. Thus, dogs are a very useful species to improve our understanding on the mechanisms involved in people's allergies and a natural model to study eczema. Animal models are frequently used to elucidate mechanisms of disease and to control for confounding factors which are present in studies with patients with spontaneously occurring disease and to test new therapies that can be beneficial in both species. It has been found that drugs useful in one species can also have benefits in other species highlighting the importance of a comprehensive understanding of diseases across species and the value of comparative studies. The purpose of the current article is to review allergic diseases across species and to focus on how these diseases compare to the counterpart in people.

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Canine Models of Atopic Dermatitis: A Useful Tool with Untapped Potential

Cited by 135 publications

References 42 publications

Characterization of Canine Filaggrin: Gene Structure and Protein Expression in Dog Skin

Characterization of Canine Filaggrin: Gene Structure and Protein Expression in Dog Skin

Activity, Expression and Genetic Variation of Canine β-Defensin 103: A Multifunctional Antimicrobial Peptide in the Skin of Domestic Dogs

Animal Models of Allergic Diseases

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