title: Two ENU-induced alleles of Atp2b2 cause deafness in mice.
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.
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia. marina.carpinelli@mcri.edu.au
authors.forename: Marina R
authors.initials: MR
authors.lastname: Carpinelli
authors.forename: Michael G
authors.initials: MG
authors.lastname: Manning
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Kile
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Burt
authors.forename: A Burt
authors.initials: AB
authors.lastname: Rachel
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D033481:Chromosomes, Mammalian / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D005038:Ethylnitrosourea; D008040:Genetic Linkage; D006198:Hair Cells, Auditory / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation / Q000235:genetics
chemical_list: D053499:Plasma Membrane Calcium-Transporting ATPases; C506959:Atp2b2 protein, mouse; D005038:Ethylnitrosourea