TY - JOUR
T1 - Mutation at the Evi1 locus in Junbo mice causes susceptibility to otitis media
AU - Parkinson, Nicholas
AU - Hardisty-Hughes, Rachel E.
AU - Tateossian, Hilda
AU - Tsai, Hsun Tien
AU - Brooker, Debra
AU - Morse, Sue
AU - Lalane, Zuzanna
AU - MacKenzie, Francesca
AU - Fray, Martin
AU - Glenister, Pete
AU - Woodward, Anne Marie
AU - Polley, Sian
AU - Barbaric, Ivana
AU - Dear, Neil
AU - Hough, Tertius A.
AU - Hunter, A. Jackie
AU - Cheeseman, Michael T.
AU - Brown, Steve D.M.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/10
Y1 - 2006/10
N2 - Otitis media (OM), inflammation of the middle ear, remains the most common cause of hearing impairment in children. It is also the most common cause of surgery in children in the developed world. There is evidence from studies of the human population and mouse models that there is a significant genetic component predisposing to OM, yet nothing is known about the underlying genetic pathways involved in humans. We identified an N-ethyl-N-nitrosourea-induced dominant mouse mutant Junbo with hearing loss due to chronic suppurative OM and otorrhea. This develops from acute OM that arises spontaneously in the postnatal period, with the age of onset and early severity dependent on the microbiological status of the mice and their air quality. We have identified the causal mutation, a missense change in the C-terminal zinc finger region of the transcription factor Evi1. This protein is expressed in middle ear basal epithelial cells, fibroblasts, and neutrophil leukocytes at postnatal day 13 and 21 when inflammatory changes are underway. The identification and characterization of the Junbo mutant elaborates a novel role for Evi1 in mammalian disease and implicates a new pathway in genetic predisposition to OM.
AB - Otitis media (OM), inflammation of the middle ear, remains the most common cause of hearing impairment in children. It is also the most common cause of surgery in children in the developed world. There is evidence from studies of the human population and mouse models that there is a significant genetic component predisposing to OM, yet nothing is known about the underlying genetic pathways involved in humans. We identified an N-ethyl-N-nitrosourea-induced dominant mouse mutant Junbo with hearing loss due to chronic suppurative OM and otorrhea. This develops from acute OM that arises spontaneously in the postnatal period, with the age of onset and early severity dependent on the microbiological status of the mice and their air quality. We have identified the causal mutation, a missense change in the C-terminal zinc finger region of the transcription factor Evi1. This protein is expressed in middle ear basal epithelial cells, fibroblasts, and neutrophil leukocytes at postnatal day 13 and 21 when inflammatory changes are underway. The identification and characterization of the Junbo mutant elaborates a novel role for Evi1 in mammalian disease and implicates a new pathway in genetic predisposition to OM.
UR - http://www.scopus.com/inward/record.url?scp=33750442875&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.0020149
DO - 10.1371/journal.pgen.0020149
M3 - Article
C2 - 17029558
AN - SCOPUS:33750442875
SN - 1553-7390
VL - 2
SP - 1556
EP - 1564
JO - PLoS Genetics
JF - PLoS Genetics
IS - 10
ER -