Investigation of sodium phenylbutyrate (NaPB) as a chemical chaperone for the treatment of Mct8-deficient mouse models

单羧酸转运蛋白8（MCT 8）是甲状腺激素的特异性转运蛋白，广泛表达于细胞和组织中。MCT 8的失活突变导致严重的精神发育迟滞。目前，没有足够的治疗方法来治疗MCT 8缺陷。Mct 8和Oatp 1c 1缺陷的小鼠复制了MCT 8缺陷患者的几个特征。治疗方案依赖于拟甲状腺药物，并在Mct 8/Oatp 1c 1双缺陷小鼠中进行了测试。苯丁酸钠（NaPB）是一种化学伴侣，可在过表达细胞模型和分化的人类诱导多能干细胞（iPSC）中挽救几种致病性Mct 8突变的功能。在这里，我们想研究NaPB在三种携带不同致病性Mct 8点突变的小鼠模型中的作用。

The monocarboxylate transporter 8 (MCT8) is a specific transporter for thyroid hormones widely expressed in cells and tissues. Inactivating mutations in MCT8 lead to severe psychomotor retardation. At the moment, there is no adequate therapy to treat MCT8 deficiency.Mice deficient in Mct8 and Oatp1c1 replicate several features of MCT8 deficient patients. Treatment options rely on thyromimetic agents and are tested in Mct8/Oatp1c1 double-deficient mice.Sodium phenylbutyrate (NaPB) is a chemical chaperone that rescues the function of several pathogenic MCT8 mutations in an over-expressing cell model and differentiated human induced pluripotent stem cells (iPSC).Here we want to investigate the effect of NaPB in three mouse models carrying different pathogenic Mct8 point mutations.