The homeobox gene Emx2 underlies middle ear and inner ear defects in the deaf mouse mutant pardon.
The semi-dominantly inherited mouse mutation pardon (Pdo) was isolated due to the lack of a Preyer reflex (ear flick) in response to sound from a large-scale N -ethyl- N -nitrosourea (ENU) mutagenesis programme. Dissection of the middle ear revealed malformations in all three ossicles, rendering the ossicular chain incomplete. Hair cell counts in the apical turn of the organ of Corti revealed a significant 22.7% increase in the number of outer hair cells. Raised compound action potential thresholds in Pdo/+ mutants suggested a combined sensorineural/conductive hearing loss. We show that a missense mutation in the homeobox gene Emx2 is responsible for these defects, identifying a new function for this gene in the development of specific structures in the ear.
Rhodes
Charlotte R
CR
MRC Institute of Hearing Research, University Park, Nottingham, NG7 2RD, UK.
Parkinson
Nicholas
N
Tsai
Hsun
H
Brooker
Debra
D
Mansell
Siobhan
S
Spurr
Nigel
N
Hunter
A Jackie
AJ
Steel
Karen P
KP
Brown
Steve D M
SD
D000200:Action Potentials / Q000235:genetics; D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D003051:Cochlea / Q000002:abnormalities / Q000473:pathology* / Q000503:physiopathology; D004429:Ear Ossicles / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology; D004432:Ear, Middle / Q000002:abnormalities / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018072:Hair Cells, Auditory, Outer / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology; D006314:Hearing Loss, Conductive / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins
D018398:Homeodomain Proteins; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins