header logo image header logo text
Downloads Login
Research
General Information
ZIRC
ZFIN ID: ZDB-PUB-170706-7
New role of LRP5, associated with non-syndromic autosomal recessive hereditary hearing loss
Xia, W., Hu, J., Liu, F., Ma, J., Sun, S., Zhang, J., Jin, K., Huang, J., Jiang, N., Wang, X., Li, W., Ma, Z., Ma, D.
Date: 2017
Source: Human Mutation 38(10): 1421-1431 (Journal)
Registered Authors: Wang, Xu
Keywords: Hereditary hearing loss, LRP5, Non syndromic hearing loss, Wnt signaling pathway
MeSH Terms:
  • Animals
  • Cell Proliferation/genetics
  • Disease Models, Animal
  • Ear, Inner/pathology*
  • Female
  • Gene Knockdown Techniques
  • Hair Cells, Auditory/pathology*
  • Hearing Loss, Sensorineural/genetics*
  • Hearing Loss, Sensorineural/physiopathology
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-5/genetics*
  • Male
  • Morpholinos/genetics
  • Mutation
  • Pedigree
  • Whole Exome Sequencing
  • Wnt Signaling Pathway/genetics
  • Zebrafish/genetics
PubMed: 28677207 Full text @ Hum. Mutat.
FIGURES
ABSTRACT
Human hearing loss is a common neurosensory disorder about which many basic research and clinically relevant questions are unresolved. And at least 50% of hearing loss are due to a genetic etiology. Although hundreds of genes have been reported, there were still hundreds of related deafness genes to be found. Clinical, genetic, and functional investigations were performed to identify the causative mutation in a distinctive Chinese family with post-lingual non-syndromic sensorineural hearing loss. Whole-exome sequencing identified lipoprotein receptor-related protein 5 (LRP5), a member of the low-density lipoprotein receptor family, as the causative gene in this family. In the zebrafish model, lrp5 downregulation using morpholinos led to significant abnormalities in zebrafish inner ear and lateral line neuromasts and contributed, to some extent, to disabilities in hearing and balance. Rescue experiments showed that LRP5 mutation is associated with hearing loss. Knocking down lrp5 in zebrafish results in reduced expression of several genes linked to Wnt signaling pathway and decreased cell proliferation when compared with those in wild type zebrafish. In conclusion, the LRP5 mutation influences cell proliferation through the Wnt signaling pathway, thereby reducing the number of supporting cells and hair cells and leading to non-syndromic hearing loss in this Chinese family. This article is protected by copyright. All rights reserved.
ADDITIONAL INFORMATION