PDF(Pubmed)
Abstract：
UNASSIGNED: Duchenne muscular dystrophy (DMD) is a hereditary neuromuscular disorder caused by mutation in the dystrophin gene (DMD) on the X chromosome. Female DMD carriers occasionally exhibit symptoms such as muscle weakness and heart failure. Here, we investigated the characteristics and representativeness of female DMD carrier (DMD-XKOXWT) pigs as a suitable disease model.
UNASSIGNED: In vitro fertilization using sperm from a DMD-XKOY↔XWTXWT chimeric boar yielded DMD-XKOXWT females, which were used to generate F2 and F3 progeny, including DMD-XKOXWT females. F1-F3 piglets were genotyped and subjected to biochemical analysis for blood creatine kinase (CK), aspartate aminotransferase, and lactate dehydrogenase. Skeletal muscle and myocardial tissue were analyzed for the expression of dystrophin and utrophin, as well as for lymphocyte and macrophage infiltration.
UNASSIGNED: DMD-XKOXWT pigs exhibited various characteristics common to human DMD carrier patients, namely, asymptomatic hyperCKemia, dystrophin expression patterns in the skeletal and cardiac muscles, histopathological features of skeletal muscle degeneration, myocardial lesions in adulthood, and sporadic death. Pathological abnormalities observed in the skeletal muscles in DMD-XKOXWT pigs point to a frequent incidence of pathological abnormalities in the musculoskeletal tissues of latent DMD carriers. Our findings suggest a higher risk of myocardial abnormalities in DMD carrier women than previously believed.
UNASSIGNED: We demonstrated that DMD-XKOXWT pigs could serve as a suitable large animal model for understanding the pathogenic mechanism in DMD carriers and developing therapies for female DMD carriers.
UNASSIGNED: In vitro fertilization using sperm from a DMD-XKOY↔XWTXWT chimeric boar yielded DMD-XKOXWT females, which were used to generate F2 and F3 progeny, including DMD-XKOXWT females. F1-F3 piglets were genotyped and subjected to biochemical analysis for blood creatine kinase (CK), aspartate aminotransferase, and lactate dehydrogenase. Skeletal muscle and myocardial tissue were analyzed for the expression of dystrophin and utrophin, as well as for lymphocyte and macrophage infiltration.
UNASSIGNED: DMD-XKOXWT pigs exhibited various characteristics common to human DMD carrier patients, namely, asymptomatic hyperCKemia, dystrophin expression patterns in the skeletal and cardiac muscles, histopathological features of skeletal muscle degeneration, myocardial lesions in adulthood, and sporadic death. Pathological abnormalities observed in the skeletal muscles in DMD-XKOXWT pigs point to a frequent incidence of pathological abnormalities in the musculoskeletal tissues of latent DMD carriers. Our findings suggest a higher risk of myocardial abnormalities in DMD carrier women than previously believed.
UNASSIGNED: We demonstrated that DMD-XKOXWT pigs could serve as a suitable large animal model for understanding the pathogenic mechanism in DMD carriers and developing therapies for female DMD carriers.
摘要：
■杜氏肌营养不良症（DMD）是一种遗传性神经肌肉疾病，由X染色体上的肌营养不良蛋白基因（DMD）突变引起。女性DMD携带者偶尔表现出诸如肌肉无力和心力衰竭的症状。这里,我们调查了雌性DMD携带者（DMD-XKOXWT）猪作为合适的疾病模型的特征和代表性。
■使用DMD-XKOYXWTXWT嵌合公猪的精子进行体外受精，产生了DMD-XKOXWT雌性，用于产生F2和F3后代，包括DMD-XKOXWT女性。对F1-F3仔猪进行基因分型并进行血液肌酸激酶（CK）的生化分析，天冬氨酸转氨酶,和乳酸脱氢酶.分析骨骼肌和心肌组织中肌养蛋白和肌养蛋白的表达,以及淋巴细胞和巨噬细胞浸润。
■DMD-XKOXWT猪表现出人类DMD携带者患者共有的各种特征，即,无症状的高CK血症，骨骼肌和心肌中的肌营养不良蛋白表达模式，骨骼肌变性的组织病理学特征，成年后的心肌损伤，和零星的死亡。在DMD-XKOXWT猪的骨骼肌中观察到的病理异常表明潜伏DMD携带者的肌肉骨骼组织中病理异常的频繁发生。我们的发现表明，DMD携带者女性发生心肌异常的风险比以前认为的要高。
■我们证明了DMD-XKOXWT猪可以作为了解DMD携带者致病机制和开发雌性DMD携带者治疗方法的合适的大型动物模型。
■使用DMD-XKOYXWTXWT嵌合公猪的精子进行体外受精，产生了DMD-XKOXWT雌性，用于产生F2和F3后代，包括DMD-XKOXWT女性。对F1-F3仔猪进行基因分型并进行血液肌酸激酶（CK）的生化分析，天冬氨酸转氨酶,和乳酸脱氢酶.分析骨骼肌和心肌组织中肌养蛋白和肌养蛋白的表达,以及淋巴细胞和巨噬细胞浸润。
■DMD-XKOXWT猪表现出人类DMD携带者患者共有的各种特征，即,无症状的高CK血症，骨骼肌和心肌中的肌营养不良蛋白表达模式，骨骼肌变性的组织病理学特征，成年后的心肌损伤，和零星的死亡。在DMD-XKOXWT猪的骨骼肌中观察到的病理异常表明潜伏DMD携带者的肌肉骨骼组织中病理异常的频繁发生。我们的发现表明，DMD携带者女性发生心肌异常的风险比以前认为的要高。
■我们证明了DMD-XKOXWT猪可以作为了解DMD携带者致病机制和开发雌性DMD携带者治疗方法的合适的大型动物模型。
