The Lily and Avrahamo Gildor Chair for the Investigation of Growth Factors; The Elton Laboratory for Neuroendocrinology; Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Sagol School of Neuroscience and Adams Super Center for Brain Studies, Tel Aviv University, 69978, Tel Aviv, Israel.
Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Neurochem Res. 2019 Jun;44(6):1494-1507. doi: 10.1007/s11064-019-02723-6. Epub 2019 Jan 18.
Autism is a wide spread neurodevelopmental disorder with growing morbidity rates, affecting more boys than girls worldwide. Activity-dependent neuroprotective protein (ADNP) was recently recognized as a leading gene accounted for 0.17% of autism spectrum disorder (ASD) cases globally. Respectively, mutations in the human ADNP gene (ADNP syndrome), cause multi-system body dysfunctions with apparent ASD-related traits, commencing as early as childhood. The Adnp haploinsufficient (Adnp) mouse model was researched before in relations to Alzheimer's disease and autism. Adnp mice suffer from deficient social memory, vocal and motor impediments, irregular tooth eruption and short stature, all of which corresponds with reported phenotypes in patients with the ADNP syndrome. Recently, a more elaborated description of the ADNP syndrome was published, presenting impediments such as hearing disabilities in > 10% of the studied children. Irregular auditory brainstem response (ABR) has been connected to ASD-related cases and has been suggested as a potential hallmark for autism, allowing diagnosis of ASD risk and early intervention. Herein, we present detriment hearing in the Adnp mice with atypical ABR and significant protein expression irregularities that coincides with ASD and hearing loss studies in the brain.
自闭症是一种广泛存在的神经发育障碍，发病率不断上升，全球范围内男孩比女孩受影响更多。活性依赖性神经保护蛋白（ADNP）最近被认为是导致全球 0.17%自闭症谱系障碍（ASD）病例的主要基因。相应地，人类 ADNP 基因（ADNP 综合征）的突变会导致多系统身体功能障碍，表现出明显的 ASD 相关特征，早在儿童期就开始出现。之前已经研究过 Adnp 杂合不足（Adnp）小鼠模型与阿尔茨海默病和自闭症的关系。Adnp 小鼠患有社交记忆缺陷、发声和运动障碍、牙齿不规则萌出和身材矮小，所有这些都与 ADNP 综合征患者的报告表型相对应。最近，更详细地描述了 ADNP 综合征，报告了 10%以上研究儿童的听力障碍。不规则的听觉脑干反应（ABR）与 ASD 相关病例有关，并被认为是自闭症的潜在标志，可用于诊断 ASD 风险和早期干预。在此，我们介绍了 Adnp 小鼠的听力受损情况，其 ABR 不典型，大脑中的蛋白质表达异常与 ASD 和听力损失研究相吻合。
