Mcph1-deficient mice reveal a role for MCPH1 in otitis media.
Otitis media is a common reason for hearing loss, especially in children. Otitis media is a multifactorial disease and environmental factors, anatomic dysmorphology and genetic predisposition can all contribute to its pathogenesis. However, the reasons for the variable susceptibility to otitis media...
Main Authors: | , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2013-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3596415?pdf=render |
id |
doaj-48ee8e9591c54975b473804e639fb7a1 |
---|---|
record_format |
Article |
spelling |
doaj-48ee8e9591c54975b473804e639fb7a12020-11-25T02:08:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5815610.1371/journal.pone.0058156Mcph1-deficient mice reveal a role for MCPH1 in otitis media.Jing ChenNeil InghamSimon ClareClaire RaisenValerie E VancollieOzama IsmailRebecca E McIntyreStephen H TsangVinit B MahajanGordon DouganDavid J AdamsJacqueline K WhiteKaren P SteelOtitis media is a common reason for hearing loss, especially in children. Otitis media is a multifactorial disease and environmental factors, anatomic dysmorphology and genetic predisposition can all contribute to its pathogenesis. However, the reasons for the variable susceptibility to otitis media are elusive. MCPH1 mutations cause primary microcephaly in humans. So far, no hearing impairment has been reported either in the MCPH1 patients or mouse models with Mcph1 deficiency. In this study, Mcph1-deficient (Mcph1(tm1a) (/tm1a) ) mice were produced using embryonic stem cells with a targeted mutation by the Sanger Institute's Mouse Genetics Project. Auditory brainstem response measurements revealed that Mcph1(tm1a) (/tm1a) mice had mild to moderate hearing impairment with around 70% penetrance. We found otitis media with effusion in the hearing-impaired Mcph1(tm1a) (/tm1a) mice by anatomic and histological examinations. Expression of Mcph1 in the epithelial cells of middle ear cavities supported its involvement in the development of otitis media. Other defects of Mcph1(tm1a) (/tm1a) mice included small skull sizes, increased micronuclei in red blood cells, increased B cells and ocular abnormalities. These findings not only recapitulated the defects found in other Mcph1-deficient mice or MCPH1 patients, but also revealed an unexpected phenotype, otitis media with hearing impairment, which suggests Mcph1 is a new gene underlying genetic predisposition to otitis media.http://europepmc.org/articles/PMC3596415?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jing Chen Neil Ingham Simon Clare Claire Raisen Valerie E Vancollie Ozama Ismail Rebecca E McIntyre Stephen H Tsang Vinit B Mahajan Gordon Dougan David J Adams Jacqueline K White Karen P Steel |
spellingShingle |
Jing Chen Neil Ingham Simon Clare Claire Raisen Valerie E Vancollie Ozama Ismail Rebecca E McIntyre Stephen H Tsang Vinit B Mahajan Gordon Dougan David J Adams Jacqueline K White Karen P Steel Mcph1-deficient mice reveal a role for MCPH1 in otitis media. PLoS ONE |
author_facet |
Jing Chen Neil Ingham Simon Clare Claire Raisen Valerie E Vancollie Ozama Ismail Rebecca E McIntyre Stephen H Tsang Vinit B Mahajan Gordon Dougan David J Adams Jacqueline K White Karen P Steel |
author_sort |
Jing Chen |
title |
Mcph1-deficient mice reveal a role for MCPH1 in otitis media. |
title_short |
Mcph1-deficient mice reveal a role for MCPH1 in otitis media. |
title_full |
Mcph1-deficient mice reveal a role for MCPH1 in otitis media. |
title_fullStr |
Mcph1-deficient mice reveal a role for MCPH1 in otitis media. |
title_full_unstemmed |
Mcph1-deficient mice reveal a role for MCPH1 in otitis media. |
title_sort |
mcph1-deficient mice reveal a role for mcph1 in otitis media. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Otitis media is a common reason for hearing loss, especially in children. Otitis media is a multifactorial disease and environmental factors, anatomic dysmorphology and genetic predisposition can all contribute to its pathogenesis. However, the reasons for the variable susceptibility to otitis media are elusive. MCPH1 mutations cause primary microcephaly in humans. So far, no hearing impairment has been reported either in the MCPH1 patients or mouse models with Mcph1 deficiency. In this study, Mcph1-deficient (Mcph1(tm1a) (/tm1a) ) mice were produced using embryonic stem cells with a targeted mutation by the Sanger Institute's Mouse Genetics Project. Auditory brainstem response measurements revealed that Mcph1(tm1a) (/tm1a) mice had mild to moderate hearing impairment with around 70% penetrance. We found otitis media with effusion in the hearing-impaired Mcph1(tm1a) (/tm1a) mice by anatomic and histological examinations. Expression of Mcph1 in the epithelial cells of middle ear cavities supported its involvement in the development of otitis media. Other defects of Mcph1(tm1a) (/tm1a) mice included small skull sizes, increased micronuclei in red blood cells, increased B cells and ocular abnormalities. These findings not only recapitulated the defects found in other Mcph1-deficient mice or MCPH1 patients, but also revealed an unexpected phenotype, otitis media with hearing impairment, which suggests Mcph1 is a new gene underlying genetic predisposition to otitis media. |
url |
http://europepmc.org/articles/PMC3596415?pdf=render |
work_keys_str_mv |
AT jingchen mcph1deficientmicerevealaroleformcph1inotitismedia AT neilingham mcph1deficientmicerevealaroleformcph1inotitismedia AT simonclare mcph1deficientmicerevealaroleformcph1inotitismedia AT claireraisen mcph1deficientmicerevealaroleformcph1inotitismedia AT valerieevancollie mcph1deficientmicerevealaroleformcph1inotitismedia AT ozamaismail mcph1deficientmicerevealaroleformcph1inotitismedia AT rebeccaemcintyre mcph1deficientmicerevealaroleformcph1inotitismedia AT stephenhtsang mcph1deficientmicerevealaroleformcph1inotitismedia AT vinitbmahajan mcph1deficientmicerevealaroleformcph1inotitismedia AT gordondougan mcph1deficientmicerevealaroleformcph1inotitismedia AT davidjadams mcph1deficientmicerevealaroleformcph1inotitismedia AT jacquelinekwhite mcph1deficientmicerevealaroleformcph1inotitismedia AT karenpsteel mcph1deficientmicerevealaroleformcph1inotitismedia |
_version_ |
1724925207569760256 |