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首页> 外文期刊>PLoS Genetics >Recessive missense LAMP3 variant associated with defect in lamellar body biogenesis and fatal neonatal interstitial lung disease in dogs
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Recessive missense LAMP3 variant associated with defect in lamellar body biogenesis and fatal neonatal interstitial lung disease in dogs

机译：隐性畸形<斜斜体>灯3 狗缺陷相关的缺陷和致命的新生儿间质性肺病

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Neonatal interstitial lung diseases due to abnormal surfactant biogenesis are rare in humans and have never been reported as a spontaneous disorder in animals. We describe here a novel lung disorder in Airedale Terrier (AT) dogs with clinical symptoms and pathology similar to the most severe neonatal forms of human surfactant deficiency. Lethal hypoxic respiratory distress and failure occurred within the first days or weeks of life in the affected puppies. Transmission electron microscopy of the affected lungs revealed maturation arrest in the formation of lamellar bodies (LBs) in the alveolar epithelial type II (AECII) cells. The secretory organelles were small and contained fewer lamellae, often in combination with small vesicles surrounded by an occasionally disrupted common limiting membrane. A combined approach of genome-wide association study and whole exome sequencing identified a recessive variant, c.1159G&A, p.(E387K), in LAMP3 , a limiting membrane protein of the cytoplasmic surfactant organelles in AECII cells. The substitution resides in the LAMP domain adjacent to a conserved disulfide bond. In summary, this study describes a novel interstitial lung disease in dogs, identifies a new candidate gene for human surfactant dysfunction and brings important insights into the essential role of LAMP3 in the process of the LB formation.
机译：由于异常的表面活性剂生物发生，新生儿间质性肺病是人类罕见的，并且从未被报告为动物的自发疾病。我们在这里描述了Airedale Terrier（AT）狗的新型肺部障碍，临床症状和病理学类似于最严重的新生儿形式的人类活性剂缺乏。受影响小狗的生命的第一天或数周内发生致命缺氧呼吸窘迫和失败。受影响的肺的透射电子显微镜显微镜揭示了肺泡上皮型II（AECII）细胞中的层状体（LBS）的形成。分泌细胞器小并且含有更少的薄片，通常与偶尔破碎的共同限制膜包围的小囊泡组合。基因组关联研究的组合方法和全外末序列测序鉴定了一个隐性变体，C.1159G＆GT; A，p。（E387K），灯3中的细胞质表面活性剂细胞器的限制膜蛋白。替代在于保守的二硫键相邻的灯畴。总之，本研究描述了一种新型间质性肺病犬，鉴定了人类表面活性剂功能障碍的新候选基因，并在LB形成过程中为灯3的基本作用带来了重要的见解。

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