Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, the Netherlands.
Connect Tissue Res. 2011 Oct;52(5):422-32. doi: 10.3109/03008207.2010.551616. Epub 2011 Mar 15.
Tenascin-X (TNX) is an extracellular matrix (ECM) glycoprotein, the absence of which in humans leads to a recessive form of Ehlers-Danlos syndrome (EDS), a group of inherited connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. A mouse model of TNX-deficient type EDS has been used to characterize the dermatological, orthopedic, and obstetrical features. The growing insight in the clinical overlap between myopathies and inherited connective tissue disorders asks for a study of the muscular characteristics of inherited connective tissue diseases. Therefore, this study aims to define the muscular phenotype of TNX knockout (KO) mice.
We performed a comprehensive study on the muscular phenotype of these TNX KO mice, consisting of standardized clinical assessment, muscle histology, and gene expression profiling of muscle tissue. Furthermore, peripheral nerve composition was studied by histology and electron microscopy.
The main findings are the presence of mild muscle weakness, mild myopathic features on histology, and functional upregulation of genes encoding proteins involved in ECM degradation and synthesis. Additionally, sciatic nerve samples showed mildly reduced collagen fibril density of endoneurium.
The muscular phenotype of TNX KO mice consists of mild muscle weakness with histological signs of myopathy and of increased turnover of the ECM in muscle. Furthermore, mildly reduced diameter of myelinated fibers and reduction of collagen fibril density of endoneurium may correspond with polyneuropathy in TNX-deficient EDS patients. This comprehensive assessment can serve as a starting point for further investigations on neuromuscular function in TNX KO mice.
Tenascin-X（TNX）是细胞外基质（ECM）糖蛋白，人类中该蛋白的缺失会导致 Ehlers-Danlos 综合征（EDS）的隐性形式，这是一组遗传性结缔组织疾病，其特征为关节过度活动、皮肤过度伸展和组织脆弱。已经使用 TNX 缺陷型 EDS 的小鼠模型来描述皮肤、骨科和产科特征。肌肉病和遗传性结缔组织疾病之间的临床重叠的认识不断提高，因此需要研究遗传性结缔组织疾病的肌肉特征。因此，本研究旨在定义 TNX 敲除（KO）小鼠的肌肉表型。
我们对这些 TNX KO 小鼠的肌肉表型进行了全面研究，包括标准化临床评估、肌肉组织学和基因表达谱分析。此外，还通过组织学和电子显微镜研究了周围神经组成。
主要发现是存在轻度肌肉无力、组织学上存在轻微的肌病特征以及编码参与 ECM 降解和合成的蛋白质的基因的功能上调。此外，坐骨神经样本显示神经内膜胶原纤维密度轻度降低。
TNX KO 小鼠的肌肉表型包括轻度肌肉无力，组织学上有肌病迹象，以及肌肉 ECM 周转率增加。此外，髓鞘纤维直径轻度减小和神经内膜胶原纤维密度降低可能与 TNX 缺陷型 EDS 患者的多发性神经病相对应。这种全面评估可以作为进一步研究 TNX KO 小鼠神经肌肉功能的起点。
