title: Identification of a novel point mutation of mouse Atp2b2 induced by N-ethyl-N-nitrosourea mutagenesis.
abstract: N-ethyl-N-nitrosourea (ENU)-induced mutagenesis is an important approach in the study of gene function and the establishment of human disease models. Here we report an ENU-induced mutation, Elfin, as a mouse model with hearing loss. Homozygous mutants were deaf and displayed severe ataxia, while heterozygous mice had a significant hearing loss. Histological analysis of the inner ear revealed that Elfin had progressive degeneration of the organ of Corti, spiral ganglion cells and an absence of otoconia in the vestibular system. The new mutation was mapped to chromosome 6 between microsatellite markers D6Mit39 and D6Mit254, where the Ca(2+)-ATPase type 2 (Atp2b2) gene resides. Sequence analysis revealed a unique T-to-A transition mutation at amino acid 655 resulting in Ile-to-Asn substitution. These results for the Elfin mutant confirm the role of ATP2B2 in balance, hearing and formation of otoconia and suggest it may serve as a new model of human hereditary hearing loss.
authors.affiliation: Department of Otolaryngology and Head & Neck Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Zixing
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiwen
authors.initials: X
authors.lastname: Xiong
authors.forename: Xingxing
authors.initials: X
authors.lastname: Gu
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Xia
authors.initials: X
authors.lastname: Gao
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000473:pathology; D005038:Ethylnitrosourea; D016057:Evoked Potentials, Auditory, Brain Stem; D034381:Hearing Loss / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics* / Q000502:physiology; D017354:Point Mutation
chemical_list: D053499:Plasma Membrane Calcium-Transporting ATPases; C506959:Atp2b2 protein, mouse; D005038:Ethylnitrosourea