Haplotype sharing excludes canine orthologous <i>Filaggrin</i> locus in atopy in West Highland White Terriers

Roque, Joana; O’Leary, C. A.; Kyaw-Tanner, Myat T.; Latter, Melanie; Mason, Kenneth; Shipstone, Michael A.; Vogelnest, Linda; Duffy, David L.

doi:10.1111/j.1365-2052.2009.01915.x

Cited by 29 publications

(27 citation statements)

References 13 publications

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“…Further, in certain breeds (e.g. WHWTs) any filaggrin mutations could have a small effect size on the phenotype, and thus not affect mRNA expression and/or cause obvious structural/histopathological epidermal abnormalities [22]. Thus, while canine filaggrin mRNA and protein levels may be decreased in non-lesional skin of some dogs with AD, this finding may be breed-specific and/or not be detected in all dogs with naturally-occurring disease.…”

Section: Resultsmentioning

confidence: 99%

Real-time PCR quantification of the canine filaggrin orthologue in the skin of atopic and non-atopic dogs: a pilot study

et al. 2011

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BackgroundCanine atopic dermatitis (AD) is a common inflammatory skin disease associated with defects in the epidermal barrier, particularly in West Highland white terriers (WHWTs). It shares many similarities with human AD, and so may be a useful animal model for this disease. Epidermal dysfunction in human AD can be caused by mutations in the gene encoding the epidermal protein filaggrin (FLG) and, in some atopic patients, be associated with altered FLG mRNA and protein expression in lesional and/or non-lesional skin. In experimental models of canine AD, mRNA expression of the orthologous canine filaggrin gene may be reduced in non-lesional skin compared with healthy controls. However, there is no published data on canine filaggrin mRNA expression in the skin of dogs with naturally-occurring AD. Hence, the aim of this pilot study was to develop a reverse transcriptase real-time PCR assay to compare filaggrin mRNA expression in the skin of atopic (n = 7) and non-atopic dogs (n = 5) from five breeds, including eight WHWTs.FindingsOverall, filaggrin mRNA expression in non-lesional atopic skin was decreased compared to non-lesional non-atopic skin (two fold change); however this difference was only statistically significant in the subgroup of WHWTs (P = 0.03).ConclusionsAlthough limited by the small sample size, these results indicate that, comparable to some cases of human AD, altered filaggrin mRNA expression may exist in the skin of some atopic dogs with naturally-occurring disease. Additional studies, including larger sample numbers, will be necessary to confirm this finding and to investigate whether mutations in the filaggrin gene exist and contribute to epidermal lesions of AD in dogs.

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Section: Resultsmentioning

confidence: 99%

Real-time PCR quantification of the canine filaggrin orthologue in the skin of atopic and non-atopic dogs: a pilot study

et al. 2011

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“…The mode of inheritance of canine AD has been investigated in different breeds but a precise mode of inheritance has not been established [16,17,35,36]. We attempted to determine the mode of inheritance using information on complete WHWT litters from normal parents, yet were extremely limited by the difficulty in obtaining detailed phenotypic information on complete litters.…”

Section: Discussionmentioning

confidence: 99%

“…However, although FLG mutations are associated with human AD, they do not fully account for the disease [12,13]. Investigation of the orthologous canine gene for FLG , located on canine chromosome 17 (CFA 17), in a cohort of WHWTs failed to show linkage to canine AD [16] raising the possibility that investigation of the cause of AD in dogs may uncover new candidate genes for the human condition. The study reported here aimed to identify an enriched genetic locus linked to AD in our WHWT pedigrees by testing for linkage to genetic markers across the entire genome.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide linkage study of atopic dermatitis in West Highland White Terriers

et al. 2011

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BackgroundCanine atopic dermatitis (AD) is a common, heritable, chronic allergic skin condition prevalent in the West Highland White Terrier (WHWT). In canine AD, environmental allergens trigger an inflammatory response causing visible skin lesions and chronic pruritus that can lead to secondary bacterial and yeast infections. The disorder shares many of the clinical and histopathological characteristics of human AD and represents an animal model of this disorder that could be used to further elucidate genetic causes of human AD. Microsatellite markers genotyped in families of WHWTs affected with AD were used to perform a genome-wide linkage study in order to isolate chromosomal regions associated with the disorder.ResultsBlood samples and health questionnaires were collected from 108 WHWTs spanning three families. A linkage simulation using these 108 dogs showed high power to detect a highly penetrant mutation. Ninety WHWTs were genotyped using markers from the Minimal Screening Set 2 (MSS-2). Two hundred and fifty six markers were informative and were used for linkage analysis. Using a LOD score of 2.7 as a significance threshold, no chromosomal regions were identified with significant linkage to AD. LOD scores greater than 1.0 were located in a 56 cM region of chromosome 7.ConclusionsThe study was unable to detect any chromosomal regions significantly linked to canine AD. This could be a result of factors such as environmental modification of phenotype, incorrect assignment of phenotype, a mutation of low penetrance, or incomplete genome coverage. A genome-wide SNP association study in a larger cohort of WHWTs may prove more successful by providing higher density coverage and higher statistical power.

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“…On the contrary, linkage studies in West Highland White Terriers indicate the absence of such correlation (Barros Roque et al 2009). However, SC lipid abnormalities have been reported.…”

Section: Introductionmentioning

confidence: 99%

Analysis of epidermal lipids in normal and atopic dogs, before and after administration of an oral omega-6/omega-3 fatty acid feed supplement. A pilot study

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et al. 2011

Vet Res Commun

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Alterations of the lipid expression in the skin of human and canine atopic subjects may be one of the key factors in the disease development. We have analyzed the ultrastructure of the clinically uninvolved skin of atopic dogs and compared it with the lipid composition of their tape-stripped stratum corneum (SC). The effect of a 2 month treatment of atopic dogs by food supplementation with a mixture of essential fatty acids was evaluated on skin samples taken before and after the treatment period. Electron microscopy revealed that the non-lesional skin of atopic dogs exhibited an abnormal and largely incomplete structure of the lamellar lipids with little cohesion between the corneocyte strata. The SC of atopic dogs was characterized by a significant decrease in the lipid content when compared to the healthy controls. Following oral supplementation with the mixture of essential fatty acids, the overall lipid content of the SC markedly increased. This feature was observed both with the free and, most importantly, with the protein-bound lipids (cholesterol, fatty acids and ceramides), the latter constituting the corneocyte-bound scaffold for ordinate organisation of the extracellular lipid bi-layers. Indeed, the semi-quantitative electron microscopy study revealed that the treatment resulted in a significantly improved organization of the lamellar lipids in the lower SC, comparable to that of the healthy dogs. Our results indicate the potential interest of long-term alimentary supplementation with omega-6 and omega-3 essential fatty acids in canine atopic dermatitis.

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Haplotype sharing excludes canine orthologous Filaggrin locus in atopy in West Highland White Terriers

Cited by 29 publications

References 13 publications

Real-time PCR quantification of the canine filaggrin orthologue in the skin of atopic and non-atopic dogs: a pilot study

Real-time PCR quantification of the canine filaggrin orthologue in the skin of atopic and non-atopic dogs: a pilot study

Genome-wide linkage study of atopic dermatitis in West Highland White Terriers

Analysis of epidermal lipids in normal and atopic dogs, before and after administration of an oral omega-6/omega-3 fatty acid feed supplement. A pilot study

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