Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Vet Dermatol. 2024 Dec;35(6):617-625. doi: 10.1111/vde.13285. Epub 2024 Aug 8.
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.
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.
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.
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.
Dogs with TGM1-deficient ARCI have an impaired skin barrier. Topical therapy can partially repair the barrier defect.
常染色体隐性遗传性鱼鳞病导致结构或生化改变，损害皮肤屏障功能。
假设/目的：评估（1）具有常染色体隐性先天性鱼鳞病（ARCI）的杰克罗素梗一窝的表型和基因型，以及（2）有缺陷的皮肤屏障，并确定局部神经酰胺是否可以调节屏障。
一只健康的母犬和一窝杰克罗素梗幼犬（健康公犬、受影响公犬和母犬）、一只受影响的成年杰克罗素梗和一只无关的健康杰克罗素梗。
通过检查受影响的幼犬，发现存在严重的角化缺陷。随着表型恶化，受影响的幼犬接受了 10 天的 ω-0-酰基神经酰胺局部应用。在人道安乐死之前，通过经皮水分流失（TEWL）、角质层测量和受影响犬的皮肤 pH 值评估皮肤屏障。进行了基因组测试，并通过光镜和电子显微镜分析皮肤样本。
受影响的幼犬在 TGM1（转谷氨酰胺酶 1）基因中为 1980bp LINE-1 插入的纯合子；未受影响的同窝仔犬和母犬为杂合携带者。ARCI 幼犬体重不足，具有严重的过度角化表型，运动能力受损。TEWL 在受影响的犬中明显更高。受影响幼犬的皮肤 pH 值高于正常同窝仔犬。用 ω-0-酰基神经酰胺处理皮肤可使 pH 值正常化并与同窝仔犬相匹配，并降低 TEWL。电子显微镜显示角蛋白包膜明显减弱。
TGM1 缺陷型 ARCI 犬的皮肤屏障受损。局部治疗可部分修复屏障缺陷。
