Two ENU-Induced Alleles of <i>Atp2b2</i> Cause Deafness in Mice

<div><p>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, <i>Deaf11</i> and <i>Deaf13</i>. Both contained causative mutations in <i>Atp2b2</i>, which encodes the plasma membrane calcium ATPase 2. The <i>Atp2b2</i>^{<i>Deaf11</i>} mutation leads to a p. I1023S substitution in the tenth transmembrane domain. The <i>Atp2b2</i>^{<i>Deaf13</i>} 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.</p>