Generation and characterization of a P2rx2 V60L mouse model for DFNA41.

Xiaoya Chen, Clemer Abad, Zheng-Yi Chen, Juan I Young, Channabasavaiah B Gurumurthy, Katherina Walz, Xue Zhong Liu

Human molecular genetics 2021 May 31

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P2RX2 encodes the P2X2 receptor, which is an adenosine triphosphate (ATP) gated (purinoreceptor) ion channel. P2RX2 c. 178G > T (p.V60L) mutation was previously identified in two unrelated Chinese families, as the cause of human DFNA41, a form of dominant, early-onset and progressive sensorineural hearing loss. We generated and characterized a knock-in mouse model based on human p.V60L mutation that recapitulates the human phenotype. Heterozygous KI mice started to exhibit hearing loss at 21-day-old and progressed to deafness by 6-month-old. Vestibular dysfunction was also observed in mutant mice. Abnormal morphology of the inner hair cells and ribbon synapses was progressively observed in KI animals suggesting that P2rx2 plays a role in the membrane spatial location of the ribbon synapses. These results suggest that P2rx2 is essential for acoustic information transfer, which can be the molecular mechanism related to hearing loss. © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Citation

Xiaoya Chen, Clemer Abad, Zheng-Yi Chen, Juan I Young, Channabasavaiah B Gurumurthy, Katherina Walz, Xue Zhong Liu. Generation and characterization of a P2rx2 V60L mouse model for DFNA41. Human molecular genetics. 2021 May 31;30(11):985-995