Perinatal Gjb2 gene transfer rescues hearing in a mouse model of hereditary deafness

Hum Mol Genet. 2015 Jul 1;24(13):3651-61. doi: 10.1093/hmg/ddv109. Epub 2015 Mar 23.

Abstract

Hearing loss is the most widespread sensory disorder, with an incidence of congenital genetic deafness of 1 in 1600 children. For many ethnic populations, the most prevalent form of genetic deafness is caused by recessive mutations in the gene gap junction protein, beta 2, 26 kDa (GJB2), which is also known as connexin 26 (Cx26). Despite this knowledge, existing treatment strategies do not completely recover speech perception. Here we used a gene delivery system to rescue hearing in a mouse model of Gjb2 deletion. Mice lacking Cx26 are characterized by profound deafness from birth and improper development of cochlear cells. Cochlear delivery of Gjb2 using an adeno-associated virus significantly improved the auditory responses and development of the cochlear structure. Using gene replacement to restore hearing in a new mouse model of Gjb2-related deafness may lead to the development of therapies for human hereditary deafness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cochlea / metabolism
  • Connexin 26
  • Connexins / genetics*
  • Connexins / metabolism
  • Deafness / congenital
  • Deafness / genetics*
  • Deafness / physiopathology
  • Deafness / therapy*
  • Dependovirus / genetics
  • Dependovirus / metabolism
  • Disease Models, Animal
  • Female
  • Gene Transfer Techniques
  • Genetic Therapy*
  • Hearing
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Perinatal Care

Substances

  • Connexins
  • GJB2 protein, human
  • Gjb2 protein, mouse
  • Connexin 26