Mouse provides new clue to hearing loss
4 November 2008
Progressive loss of hearing affects around six out of ten people over the age of 70. Environmental factors - such as physical damage to the ear, exposure to excessive noise levels, drugs and infections - can lead to hearing loss, but genetic influences can also play a major role. Yet we know little about the genes involved.
The research team, led by scientists from the Wellcome Trust Sanger Institute in Cambridge examined a variety of mutant mice for impaired hearing, identifying one mouse mutant called Oblivion.
Oblivion mice were either completely deaf, with the hair cells of their ears damaged at birth, or they showed progressive hearing loss during the first three months of life - their hair cells were functional at first, but degenerating later. The ear relies on hair cells to translate sounds into electrical impulses that the brain can interpret.
Further study of the mice revealed a change in one letter of a gene, Atp2b2, which codes for a calcium pump.
“Changing a specific C to a T in this gene stops it from producing a normal molecular pump that is needed to keep hair cells in the ear working efficiently by pumping excess calcium out of the cell,” said Professor Karen Steel from the Wellcome Trust Sanger Institute and senior author on the study.
Mice, like humans, inherit two copies of any gene, one from each parent. “If one copy of the Atp2b2 gene is affected, the pump works, but not well enough and hearing gradually fails; if both copies are affected, the pump hardly works at all and hearing is lost before birth,” said Professor Steel.
Although other mutations have been described, the Oblivion mutant is unique in the way it leads to hearing loss due to mutations in Atp2b2. Hearing is impaired before any physical sign of hair cell damage can be seen.
The effect mimics human progressive loss of hearing, and some instances of human hearing loss are, at least in part, due to mutation in the human form of the Atp2b2 gene.
The researchers hope that improving understanding of the genetic variants involved in hearing will lead to better diagnostics and treatments for humans with impaired hearing.
References
Spiden S L et al. The novel mouse mutation Oblivion inactivates the PMCA2 pump and causes progressive hearing loss. PLoS Genetics,4(10)e1000238.