Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America.
PLoS One. 2012;7(2):e32072. doi: 10.1371/journal.pone.0032072. Epub 2012 Feb 22.
In humans, congenital and hereditary skin diseases associated with epidermal cell-cell separation (acantholysis) are very rare, and spontaneous animal models of these diseases are exceptional. Our objectives are to report a novel congenital acantholytic dermatosis that developed in Chesapeake Bay retriever dogs. Nine affected puppies in four different litters were born to eight closely related clinically normal dogs. The disease transmission was consistent with an autosomal recessive mode of inheritance. Clinical signs occurred immediately after birth with superficial epidermal layers sloughing upon pressure. At three month of age, dogs exhibited recurrent superficial skin sloughing and erosions at areas of friction and mucocutaneous junctions; their coat was also finer than normal and there were patches of partial hair loss. At birth, histopathology revealed severe suprabasal acantholysis, which became less severe with ageing. Electron microscopy demonstrated a reduced number of partially formed desmosomes with detached and aggregated keratin intermediate filaments. Immunostaining for desmosomal adhesion molecules revealed a complete lack of staining for plakophilin-1 and anomalies in the distribution of desmoplakin and keratins 10 and 14. Sequencing revealed a homozygous splice donor site mutation within the first intron of PKP1 resulting in a premature stop codon, thereby explaining the inability to detect plakophilin-1 in the skin. Altogether, the clinical and pathological findings, along with the PKP1 mutation, were consistent with the diagnosis of ectodermal dysplasia-skin fragility syndrome with plakophilin-1 deficiency. This is the first occurrence of ectodermal dysplasia-skin fragility syndrome in an animal species. Controlled mating of carrier dogs would yield puppies that could, in theory, be tested for gene therapy of this rare but severe skin disease of children.
在人类中，与表皮细胞-细胞分离（棘层松解）相关的先天性和遗传性皮肤疾病非常罕见，并且这些疾病的自发性动物模型也很罕见。我们的目标是报告一种新的先天性棘层松解性皮肤病，该疾病发生在切萨皮克湾寻回犬中。在四个不同的窝中，有 8 只密切相关的临床正常犬共生育了 9 只受影响的幼犬。该疾病的传播符合常染色体隐性遗传模式。出生后立即出现临床症状，表皮浅层在受压时脱落。在 3 月龄时，犬表现出复发性的浅层皮肤脱落和摩擦部位及黏膜交界处的糜烂；其被毛也比正常的细，并有部分脱发斑块。出生时的组织病理学检查显示严重的基底层棘层松解，随着年龄的增长，棘层松解程度减轻。电子显微镜检查显示部分形成的桥粒数量减少，角蛋白中间丝分离和聚集。桥粒黏附分子的免疫染色显示，桥粒斑蛋白-1 完全缺失，桥粒斑蛋白和角蛋白 10、14 的分布异常。测序显示 PKP1 基因的第一个内含子中存在纯合剪接供体位点突变，导致提前终止密码子，从而解释了在皮肤中无法检测到桥粒斑蛋白-1 的原因。综上所述，临床和病理学发现以及 PKP1 突变与桥粒斑蛋白-1 缺陷型外胚层发育不良-皮肤脆弱综合征的诊断一致。这是该疾病首次在动物物种中发生。通过对携带者犬进行控制交配，理论上可以获得可用于治疗这种罕见但严重儿童皮肤病的基因治疗的幼犬。
