Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Neurosci Lett. 2020 Nov 20;739:135449. doi: 10.1016/j.neulet.2020.135449. Epub 2020 Oct 25.
Genetic defects in ribosome biogenesis result in a group of diseases called ribosomopathies. Patients with ribosomopathies manifest multiorgan phenotypes, including neurological impairments. A well-characterized ribosomopathy, Shwachman-Diamond syndrome (SDS), is mainly associated with loss-of-function mutations in the causal gene SBDS. Children with SDS have neurodevelopmental disorders; however, the neurological consequences of SBDS dysfunction remain poorly defined. In the present study, we investigated the phenotype of Drosophila melanogaster following knockdown of CG8549, the Drosophila ortholog of human SBDS, to provide evidence for the neurological consequences of reduction in physiological SBDS functions. The pan-neuron-specific knockdown of CG8549 was associated with locomotive disabilities, mechanically induced seizures, hyperactivity, learning impairments, and anatomical defects in presynaptic terminals. These results provide the first evidence of a direct link between a reduction in physiological SBDS function and neurological impairments.
核糖体生物发生的遗传缺陷导致了一组被称为核糖体病的疾病。患有核糖体病的患者表现出多种器官表型，包括神经损伤。Shwachman-Diamond 综合征（SDS）是一种特征明确的核糖体病，主要与致病基因 SBDS 的功能丧失突变有关。SDS 患儿存在神经发育障碍；然而，SBDS 功能障碍的神经后果仍未得到明确界定。在本研究中，我们通过敲低果蝇中与人 SBDS 同源的 CG8549，研究了果蝇的表型，为 SBDS 生理功能降低导致的神经后果提供了证据。全神经元特异性敲低 CG8549 与运动障碍、机械诱导的癫痫发作、过度活跃、学习障碍以及突触前末梢的解剖缺陷有关。这些结果首次提供了生理 SBDS 功能降低与神经损伤之间直接联系的证据。
