A new mutation of the Atoh1 gene in mice with normal life span allows analysis of inner ear and cerebellar phenotype in aging

PLoS One. 2013 Nov 12;8(11):e79791. doi: 10.1371/journal.pone.0079791. eCollection 2013.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Amino Acid Sequence
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / chemistry
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Cerebellum / metabolism*
  • Cerebellum / pathology
  • Chromosome Mapping
  • DNA Mutational Analysis
  • Ear, Inner / metabolism*
  • Gene Expression Regulation
  • Hair Cells, Auditory, Inner / pathology
  • Hair Cells, Auditory, Inner / ultrastructure
  • Hearing Loss / diagnosis
  • Hearing Loss / genetics
  • Hearing Loss / pathology
  • Hearing Tests
  • Longevity / genetics*
  • Mice
  • Mutation*
  • Phenotype*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Alignment

Substances

  • Atoh1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • RNA, Messenger