Elizabeth Mauldin, Charles Bradley, Margret Casal, Jason Meyer, Debra Crumrine, Sarah Kiener, Tosso Leeb, Peter M Elias
{"title":"TGM1缺陷杰克罗素梗犬常染色体隐性鱼鳞病的皮肤屏障、表型和基因型特征以及对局部神经酰胺的反应。","authors":"Elizabeth Mauldin, Charles Bradley, Margret Casal, Jason Meyer, Debra Crumrine, Sarah Kiener, Tosso Leeb, Peter M Elias","doi":"10.1111/vde.13285","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Autosomal recessive ichthyosis leads to structural or biochemical changes that impair skin barrier function.</p><p><strong>Hypothesis/objectives: </strong>To assess (1) the phenotype and genotype in a litter of Jack Russell Terriers with autosomal recessive congenital ichthyosis (ARCI), and (2) the defective skin barrier and determine if a topical ceramide can modulate the barrier.</p><p><strong>Animals: </strong>A healthy dam and litter of Jack Russell Terrier puppies (healthy male, affected male and female), one affected adult Jack Russell Terrier and one unrelated healthy Jack Russell Terrier.</p><p><strong>Materials and methods: </strong>A severe cornification defect was identified via examination of affected puppies. As the phenotype worsened, the affected puppies received a topical application of ω-0-acylceramide for 10 days. Before humane euthanasia, the skin barrier was evaluated via transepidermal water loss (TEWL), corneometry and pH in affected dogs. Genomic testing was performed, and skin samples were analysed by light and electron microscopy.</p><p><strong>Results: </strong>Affected puppies were homozygous for the 1980 bp LINE-1 insertion in the TGM1 (transglutaminase 1) gene; the unaffected littermate and the dam were heterozygous carriers. ARCI puppies were underweight and had a severe hyperkeratotic phenotype that impaired mobility. TEWL was markedly higher in affected dogs. The cutaneous pH of affected puppies was higher than the normal littermate. Treatment of the skin with ω-0-acylceramide normalised the pH to match the littermate and decreased TEWL. Electron microscopy revealed marked attenuation of the cornified envelope.</p><p><strong>Conclusions and clinical relevance: </strong>Dogs with TGM1-deficient ARCI have an impaired skin barrier. Topical therapy can partially repair the barrier defect.</p>","PeriodicalId":23599,"journal":{"name":"Veterinary dermatology","volume":" ","pages":"617-625"},"PeriodicalIF":1.9000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Skin barrier, phenotypic and genotypic characterisation of autosomal recessive ichthyosis in TGM1-deficient Jack Russell Terriers and response to topical ceramide.\",\"authors\":\"Elizabeth Mauldin, Charles Bradley, Margret Casal, Jason Meyer, Debra Crumrine, Sarah Kiener, Tosso Leeb, Peter M Elias\",\"doi\":\"10.1111/vde.13285\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Autosomal recessive ichthyosis leads to structural or biochemical changes that impair skin barrier function.</p><p><strong>Hypothesis/objectives: </strong>To assess (1) the phenotype and genotype in a litter of Jack Russell Terriers with autosomal recessive congenital ichthyosis (ARCI), and (2) the defective skin barrier and determine if a topical ceramide can modulate the barrier.</p><p><strong>Animals: </strong>A healthy dam and litter of Jack Russell Terrier puppies (healthy male, affected male and female), one affected adult Jack Russell Terrier and one unrelated healthy Jack Russell Terrier.</p><p><strong>Materials and methods: </strong>A severe cornification defect was identified via examination of affected puppies. As the phenotype worsened, the affected puppies received a topical application of ω-0-acylceramide for 10 days. Before humane euthanasia, the skin barrier was evaluated via transepidermal water loss (TEWL), corneometry and pH in affected dogs. Genomic testing was performed, and skin samples were analysed by light and electron microscopy.</p><p><strong>Results: </strong>Affected puppies were homozygous for the 1980 bp LINE-1 insertion in the TGM1 (transglutaminase 1) gene; the unaffected littermate and the dam were heterozygous carriers. ARCI puppies were underweight and had a severe hyperkeratotic phenotype that impaired mobility. TEWL was markedly higher in affected dogs. The cutaneous pH of affected puppies was higher than the normal littermate. Treatment of the skin with ω-0-acylceramide normalised the pH to match the littermate and decreased TEWL. Electron microscopy revealed marked attenuation of the cornified envelope.</p><p><strong>Conclusions and clinical relevance: </strong>Dogs with TGM1-deficient ARCI have an impaired skin barrier. Topical therapy can partially repair the barrier defect.</p>\",\"PeriodicalId\":23599,\"journal\":{\"name\":\"Veterinary dermatology\",\"volume\":\" \",\"pages\":\"617-625\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Veterinary dermatology\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://doi.org/10.1111/vde.13285\",\"RegionNum\":3,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/8 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Veterinary dermatology","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1111/vde.13285","RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/8 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"DERMATOLOGY","Score":null,"Total":0}
Skin barrier, phenotypic and genotypic characterisation of autosomal recessive ichthyosis in TGM1-deficient Jack Russell Terriers and response to topical ceramide.
Background: Autosomal recessive ichthyosis leads to structural or biochemical changes that impair skin barrier function.
Hypothesis/objectives: To assess (1) the phenotype and genotype in a litter of Jack Russell Terriers with autosomal recessive congenital ichthyosis (ARCI), and (2) the defective skin barrier and determine if a topical ceramide can modulate the barrier.
Animals: A healthy dam and litter of Jack Russell Terrier puppies (healthy male, affected male and female), one affected adult Jack Russell Terrier and one unrelated healthy Jack Russell Terrier.
Materials and methods: A severe cornification defect was identified via examination of affected puppies. As the phenotype worsened, the affected puppies received a topical application of ω-0-acylceramide for 10 days. Before humane euthanasia, the skin barrier was evaluated via transepidermal water loss (TEWL), corneometry and pH in affected dogs. Genomic testing was performed, and skin samples were analysed by light and electron microscopy.
Results: Affected puppies were homozygous for the 1980 bp LINE-1 insertion in the TGM1 (transglutaminase 1) gene; the unaffected littermate and the dam were heterozygous carriers. ARCI puppies were underweight and had a severe hyperkeratotic phenotype that impaired mobility. TEWL was markedly higher in affected dogs. The cutaneous pH of affected puppies was higher than the normal littermate. Treatment of the skin with ω-0-acylceramide normalised the pH to match the littermate and decreased TEWL. Electron microscopy revealed marked attenuation of the cornified envelope.
Conclusions and clinical relevance: Dogs with TGM1-deficient ARCI have an impaired skin barrier. Topical therapy can partially repair the barrier defect.
期刊介绍:
Veterinary Dermatology is a bi-monthly, peer-reviewed, international journal which publishes papers on all aspects of the skin of mammals, birds, reptiles, amphibians and fish. Scientific research papers, clinical case reports and reviews covering the following aspects of dermatology will be considered for publication:
-Skin structure (anatomy, histology, ultrastructure)
-Skin function (physiology, biochemistry, pharmacology, immunology, genetics)
-Skin microbiology and parasitology
-Dermatopathology
-Pathogenesis, diagnosis and treatment of skin diseases
-New disease entities