Two ENU-induced alleles of Atp2b2 cause deafness in mice

Marina R Carpinelli; Michael G Manning; Benjamin T Kile; Rachel A Burt

doi:10.1371/journal.pone.0067479

Two ENU-induced alleles of Atp2b2 cause deafness in mice

PLoS One. 2013 Jun 24;8(6):e67479. doi: 10.1371/journal.pone.0067479. Print 2013.

Authors

Marina R Carpinelli¹, Michael G Manning, Benjamin T Kile, Rachel A Burt

Affiliation

¹ Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia. [email protected]

Abstract

Over 120 loci are known to cause inherited hearing loss in humans. The deafness gene has been identified for only half of these loci. With the aim of identifying some of the remaining deafness genes, we performed an ethylnitrosourea mutagenesis screen for deaf mice. We isolated two mutants with semi-dominant hearing loss, Deaf11 and Deaf13. Both contained causative mutations in Atp2b2, which encodes the plasma membrane calcium ATPase 2. The Atp2b2 (Deaf11) mutation leads to a p. I1023S substitution in the tenth transmembrane domain. The Atp2b2 (Deaf13) mutation leads to a p. R561S substitution in the catalytic core. Mice homozygous for these mutations display profound hearing loss. Heterozygotes display mild to moderate, progressive hearing loss.

MeSH terms

Alleles*
Amino Acid Sequence
Animals
Chromosomes, Mammalian / genetics
Deafness / genetics*
Ethylnitrosourea
Genetic Linkage
Hair Cells, Auditory / metabolism
Hair Cells, Auditory / pathology
Male
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Plasma Membrane Calcium-Transporting ATPases / chemistry
Plasma Membrane Calcium-Transporting ATPases / genetics*
Plasma Membrane Calcium-Transporting ATPases / metabolism
Point Mutation / genetics

Substances

Plasma Membrane Calcium-Transporting ATPases
Atp2b2 protein, mouse
Ethylnitrosourea

Grants and funding

The authors acknowledge the financial support of the HEARing CRC (www.hearingcrc.org), established and supported under the Australian Government’s Cooperative Research Centres Program; the Victorian State Government’s Operational Infrastructure Support Program; the Australian Government’s NHMRC IRIISS (www.nhmrc.gov.au); a National Collaborative Research Infrastructure Strategy grant to the Australian Phenomics Network (www.australianphenomics.org.au); and the Garnet Passe and Rodney Williams Memorial Foundation (www.gprwmf.org.au, fellowship to MRC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.