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ORIGINAL RESEARCH article

Front. Genet.

Sec. Genetics of Common and Rare Diseases

Volume 16 - 2025 | doi: 10.3389/fgene.2025.1634493

This article is part of the Research TopicInsights in Genetics of Common and Rare Diseases 2024View all 27 articles

Functional Characterization of MFSD3 in Auditory System and Zebrafish Embryogenesis

Provisionally accepted
Ying MaYing Ma1,2,3,4,5Shiwei QiuShiwei Qiu6,7Weiqian WangWeiqian Wang8Haifeng FengHaifeng Feng1,2,3,4,5Lu ZhengLu Zheng1,2,3,4,5Ge-Ge WeiGe-Ge Wei1,2,3,4,5Hui-Yi NieHui-Yi Nie1,2,3,4,5Jin-Yuan YangJin-Yuan Yang1,2,3,4,5Yi-Jin ChenYi-Jin Chen1,2,3,4,5Pu DaiPu Dai1,2,3,4,5Xue GaoXue Gao8*Yongyi YuanYongyi Yuan1,2,3,4,5*
  • 1Senior Department of Otolaryngology Head and Neck Surgery, the 6th Medical Center of Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China
  • 2State Key Laboratory of Hearing and Balance Science, Beijing, China
  • 3National Clinical Research Center for Otolaryngologic Diseases, Beijing, China
  • 4Key Laboratory of Hearing Science, Ministry of Education, Beijing, China
  • 5Beijing Key Laboratory of Hearing Impairment Prevention and Treatment, Beijing, China
  • 6Tsinghua University School of Life Sciences, Beijing, China
  • 7Chinese Institute for Brain Research, Beijing, China
  • 8Department of Otolaryngology, PLA Rocket Force Characteristic Medical Center, Beijing, China

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The solute carriers (SLCs) are important membrane-bound transporters that regulate cellular nutrition, metabolism, homeostasis and survival. Emerging evidence highlights the critical involvement of SLCs in auditory physiology. To date, over ten SLC family members have been linked to hearing function. MFSD3 (also known as SLC33A2), is a putative plasma membrane-localized acetyl-CoA transporter regulating lipid metabolism and energy homeostasis. It has been found to be associated with the pathogenesis of neurodegenerative dementia and tumor progression. Nevertheless, its potential role in hearing remains unexplored. In this study, through qRT-PCR, we demonstrated that mfsd3 was predominantly expressed during early embryonic development in zebrafish. Morpholino-mediated mfsd3 knockdown in zebrafish induced inner ear malformations (hypoplastic otic vesicles, reduced otolith size) and hair cells loss in lateral line neuromasts. Additionally, Mfsd3 deficiency led to developmental defects (pericardial edema, body axis curvature) and impaired locomotor activity in zebrafish. The qRT-PCR analysis further revealed significant upregulation of key Wnt/β-catenin pathway components (dkk1b, wnt8a, lrp6, frzb and COX2) in mfsd3 knockdown zebrafish. Our findings suggest MFSD3 as a potential participant in auditory function and embryogenesis, with implications for understanding hearing loss pathogenesis.

Keywords: MFSD3, morpholino knockdown, Zebrafish, Auditory system, Wnt/β-catenin

Received: 24 May 2025; Accepted: 27 Aug 2025.

Copyright: © 2025 Ma, Qiu, Wang, Feng, Zheng, Wei, Nie, Yang, Chen, Dai, Gao and Yuan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Xue Gao, Department of Otolaryngology, PLA Rocket Force Characteristic Medical Center, Beijing, China
Yongyi Yuan, Senior Department of Otolaryngology Head and Neck Surgery, the 6th Medical Center of Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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