Details

Autor(en) / Beteiligte

• Song, Gyun Jee
• Gupta, Deepak Prasad
• Rahman, Md Habibur
• Park, Hwan Tae
• Al Ghouleh, Imad
• Bisello, Alessandro
• Lee, Maan‐Gee
• Park, Jae‐Yong
• Park, Hyun Ho
• Jun, Jin Hyun
• Chung, Ki Wha
• Choi, Byung‐Ok
• Suk, Kyoungho

Titel

Loss‐of‐function of EBP50 is a new cause of hereditary peripheral neuropathy: EBP50 functions in peripheral nerve system

Ist Teil von

• Glia, 2020-09, Vol.68 (9), p.1794-1809

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2020

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Finding causative genetic mutations is important in the diagnosis and treatment of hereditary peripheral neuropathies. This study was conducted to find new genes involved in the pathophysiology of hereditary peripheral neuropathy. We identified a new mutation in the EBP50 gene, which is co‐segregated with neuropathic phenotypes, including motor and sensory deficit in a family with Charcot–Marie–Tooth disease. EBP50 is known to be important for the formation of microvilli in epithelial cells, and the discovery of this gene mutation allowed us to study the function of EBP50 in the nervous system. EBP50 was strongly expressed in the nodal and paranodal regions of sciatic nerve fibers, where Schwann cell microvilli contact the axolemma, and at the growth tips of primary Schwann cells. In addition, EBP50 expression was decreased in mouse models of peripheral neuropathy. Knockout mice were used to study EBP50 function in the peripheral nervous system. Interestingly motor function deficit and abnormal histology of nerve fibers were observed in EBP50+/− heterozygous mice at 12 months of age, but not 3 months. in vitro studies using Schwann cells showed that NRG1‐induced AKT activation and migration were significantly reduced in cells overexpressing the I325V mutant of EBP50 or cells with knocked‐down EBP50 expression. In conclusion, we show for the first time that loss of function due to EBP50 gene deficiency or mutation can cause peripheral neuropathy. Motor function deficit and abnormal myelination were observed in EBP50+/− mice. NRG1‐induced AKT activation was reduced in Schwann cells overexpressing the mutant EBP50. A novel mutation in EBP50 gene was found in a peripheral neuropathic family.