title: A new mutation of the Atoh1 gene in mice with normal life span allows analysis of inner ear and cerebellar phenotype in aging.
abstract: Atoh1 is a transcription factor that regulates neural development in multiple tissues and is conserved among species. Prior mouse models of Atoh1, though effective and important in the evolution of our understanding of the gene, have been limited by perinatal lethality. Here we describe a novel point mutation of Atoh1 (designated Atoh1(trhl) ) underlying a phenotype of trembling gait and hearing loss. Histology revealed inner ear hair cell loss and cerebellar atrophy. Auditory Brainstem Response (ABR) and Distortion Product Otoacoustic Emission (DPOAE) showed functional abnormalities in the ear. Normal lifespan and fecundity of Atoh1(trhl) mice provide a complementary model to facilitate elucidation of ATOH1 function in hearing,central nervous system and cancer biology.
authors.affiliation: Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Kianoush
authors.initials: K
authors.lastname: Sheykholeslami
authors.forename: Vikrum
authors.initials: V
authors.lastname: Thimmappa
authors.forename: Casey
authors.initials: C
authors.lastname: Nava
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Bai
authors.forename: Heping
authors.initials: H
authors.lastname: Yu
authors.forename: Tihua
authors.initials: T
authors.lastname: Zheng
authors.forename: Zhaoqiang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Sheng Li
authors.initials: SL
authors.lastname: Li
authors.forename: Shuqing
authors.initials: S
authors.lastname: Liu
authors.forename: Qing Yin
authors.initials: QY
authors.lastname: Zheng
mesh_terms: D000375:Aging / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000235:genetics*; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D007758:Ear, Inner / Q000378:metabolism*; D005786:Gene Expression Regulation; D006199:Hair Cells, Auditory, Inner / Q000473:pathology / Q000648:ultrastructure; D034381:Hearing Loss / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D006320:Hearing Tests; D008136:Longevity / Q000235:genetics*; D051379:Mice; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D012333:RNA, Messenger; C500943:Atoh1 protein, mouse