PUBLICATION
IQGAP3 deficiency leads to non-syndromic hearing loss via inhibition of CDC42 enzyme activity
- Authors
- Li, Y., Dong, H., Wang, X., Qian, F., Huang, J., Hou, C., Qin, H., Liu, Y., Feng, S., Liu, W., Gao, S., Sun, C., Chen, Y., Luo, R., Dai, C., Zhang, R., Liu, H., Zhang, L., Zheng, Y., Li, N., Liu, D., Zhou, P., Hu, H.
- ID
- ZDB-PUB-250417-3
- Date
- 2025
- Source
- International journal of pediatric otorhinolaryngology 193: 112358112358 (Journal)
- Registered Authors
- Liu, Dong
- Keywords
- Hair cell, Hearing loss, Hereditary, IQGAP3
- MeSH Terms
-
- Animals
- Zebrafish
- Hearing Loss*/genetics
- Humans
- GTPase-Activating Proteins*/deficiency
- GTPase-Activating Proteins*/genetics
- Disease Models, Animal
- Male
- Female
- Mice
- cdc42 GTP-Binding Protein*/antagonists & inhibitors
- cdc42 GTP-Binding Protein*/metabolism
- HEK293 Cells
- PubMed
- 40239295 Full text @ Int. J. Pediatr. Otorhinolaryngol.
Citation
Li, Y., Dong, H., Wang, X., Qian, F., Huang, J., Hou, C., Qin, H., Liu, Y., Feng, S., Liu, W., Gao, S., Sun, C., Chen, Y., Luo, R., Dai, C., Zhang, R., Liu, H., Zhang, L., Zheng, Y., Li, N., Liu, D., Zhou, P., Hu, H. (2025) IQGAP3 deficiency leads to non-syndromic hearing loss via inhibition of CDC42 enzyme activity. International journal of pediatric otorhinolaryngology. 193:112358112358.
Abstract
Background Genetic factors are important causes of congenital hearing loss. To better understand hereditary hearing loss, we performed in-depth clinical and molecular analysis of families with congenital hearing loss and a new disease-related gene, IQGAP3, was identified in this process. This gene encodes a protein that belongs to the IQGAP family which is well known as a GTPase-activating protein involved in various cellular functions. However, there is no research on the relationship between IQGAP3 and the auditory system.
Method This study was conducted at Guangzhou Women and Children's Medical Center and Nantong University from 2019 to 2023 to confirm the relationship between defective IQGAP3 and hearing loss, and further explore the underlying molecular mechanism. We constructed the iqgap3 knockdown zebrafish model, primary mouse inner progenitor cell model and IQGAP3-knockout HEK293T cell line for this research.
Result We found that IQGAP3 deficiency led to abnormal development of the auditory system and impaired auditory function in zebrafish. In vitro studies showed that loss of this gene's function resulted in a 40.29 % reduction in EdU-positive cells and a 44.25 % decrease in Ki67-positive cells in mouse inner ear progenitor cells, indicating reduced proliferation. This can be linked with inhibition of CDC42 enzymatic activity and the blockade of the Wnt-catenin pathway.
Conclusion We identified IQGAP3 as a novel potential causative gene in hereditary hearing loss. Our findings provide important insights into the molecular basis of hereditary hearing loss.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping