Molecular functional analysis of ZBTB10, the novel candidate deafness gene associated with cochlear nerve hypoplasia

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10773
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: 独立行政法人国立病院機構(東京医療センター臨床研究センター)
• Principal Investigator: Mutai Hideki 独立行政法人国立病院機構(東京医療センター臨床研究センター), その他部局等, 研究員 (60415891)
• Co-Investigator(Kenkyū-buntansha): 難波 一徳 独立行政法人国立病院機構(東京医療センター臨床研究センター), その他部局等, 研究員 (60425684)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 内耳奇形 / 蝸牛神経 / 難聴遺伝子 / 神経芽腫細胞 / ゲノム編集 / 胎生致死

Outline of Final Research Achievements

We have identified ZBTB10 as a candidate of novel deafness gene from a patient with cochlear nerve hypoplasia using whole exome analysis. ZBTB10 appeared to be expressed in the cochlear nerve. ZBTB10 expression was increased during nerve elongation of neuroblastoma NB1 cells. Zbtb10mut/+ mouse generated by CRISPR/Cas9 showed normal hearing. Low reproduction rate and anatomical observation suggests that the gene also affect proper function of ovary. All the Zbtb10mut/mut and half the number of Zbtb10mut/+ embryos seemed to be dead by the embryonic day 14.5 (E14.5). Zbtb10 appeared to be critical for early embryogenesis. We are now conducting histochemical study focusing on development of the brain, otocyst, and primordial germ line cells at E9.5. We will accumulate, analyze the data and report the results to the public soon.

Free Research Field

分子生物学