% 0期刊文章% Akatsuki日本久保田公司%瓦伦蒂娜的名叫Emmanuele %取卡利亚%一个Marti Juanola % Fusako血清%一个Homma Shunichi % Kurenai痰迹%卡塔琳娜州Quinzii Hirano % Hirano陆生% T Fhl1 W122S突变雌性老鼠出现晚发性心肌病(P5.265) % D J神经病学2016% % P P5.265 X % V % 86% N 16补充背景:X连锁scapuloperoneal肌病(X-SPM)是一种成人慢性疾病引起的Fhl1 (LIM一半4。1)突变。首页尽管女性携带杂合的FHL1突变的影响,他们的表型是比半合温和男人。X-SPM有时与心肌病,FHL1基因突变导致孤立的心肌病,Emery-Dreifuss肌肉萎缩症,减少身体肌病,x连锁肌病姿势肌肉萎缩。FHL1被认为调解蛋白质-蛋白质之间的关系;然而,表型异质性的机制是未知的。我们以前生成的敲入小鼠模型有相同的突变(c。365 G > C, p.W122S)作为人类X-SPM患者,发现突变雄性小鼠迟发性的开发缓慢进步肌病,但不是心脏功能障碍。设计/方法:我们分析了杂合的和纯合子的雌性老鼠。结果:运动测试显示瞬时轻度肌无力(15 [percnt]减少)杂合的和纯合子的雌性老鼠在10个月,但是没有病理异常总值骨骼肌在任何年龄。超声心动图在10个月是正常的,但在20个月,突变雌性老鼠显示收缩压增加直径(野生:2.74±0.22毫米,平均±标准差; heterozygous: 3.13 ± 0.11 mm, P<0.01; homozygous: 3.08 ± 0.37 mm, P<0.05) and lower fractional shortening (wild: 31.1 ± 4.4[percnt], mean ± SD; heterozygous: 22.7 ± 2.5[percnt], P<0.01; homozygous: 22.4 ± 6.9[percnt], P<0.01). Histological analysis of heart revealed frequent extraordinarily large “box-shaped” nuclei in mutant female mice. Western blot demonstrated decreased Fhl1 protein levels in double mutant female mice in heart, but not in skeletal muscle. Proteomic analysis of heart from 20 month-old double mutant female mice suggests that integrin signaling pathway is involved in cardiac dysfunction in this mouse model. CONCLUSIONS:Fhl1 W122S female mice manifest late-onset cardiac dysfunction. This is the first mouse model of FHL1-related cardiomyopathy.Disclosure: Dr. Kubota has nothing to disclose. Dr. Emmanuele has nothing to disclose. Dr. Kariya has nothing to disclose. Dr. Juanola has nothing to disclose. Dr. Sera has nothing to disclose. Dr. Homma has nothing to disclose. Dr. Tanji has nothing to disclose. Dr. Quinzii Hirano has nothing to disclose. Dr. Hirano has nothing to disclose.Wednesday, April 20 2016, 8:30 am-7:00 pm %U