title: Sh3pxd2b mice are a model for craniofacial dysmorphology and otitis media.
abstract: Craniofacial defects that occur through gene mutation during development increase vulnerability to eustachian tube dysfunction. These defects can lead to an increased incidence of otitis media. We examined the effects of a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) on the progression of otitis media and hearing impairment at various developmental stages. We found that all mice that had the Sh3pxd2b(nee) mutation went on to develop craniofacial dysmorphologies and subsequently otitis media, by as early as 11 days of age. We found noteworthy changes in cilia and goblet cells of the middle ear mucosa in Sh3pxd2b(nee) mutant mice using scanning electronic microscopy. By measuring craniofacial dimensions, we determined for the first time in an animal model that this mouse has altered eustachian tube morphology consistent with a more horizontal position of the eustachian tube. All mutants were found to have hearing impairment. Expression of TNF-α and TLR2, which correlates with inflammation in otitis media, was up-regulated in the ears of mutant mice when examined by immunohistochemistry and semi-quantitative RT-PCR. The mouse model with a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) mirrors craniofacial dysmorphology and otitis media in humans.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Cong
authors.initials: C
authors.lastname: Tian
authors.forename: Zhi-guang
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Feng-chan
authors.initials: FC
authors.lastname: Han
authors.forename: Rami
authors.initials: R
authors.lastname: Azem
authors.forename: Heping
authors.initials: H
authors.lastname: Yu
authors.forename: Ye
authors.initials: Y
authors.lastname: Zheng
authors.forename: Ge
authors.initials: G
authors.lastname: Jin
authors.forename: James E
authors.initials: JE
authors.lastname: Arnold
authors.forename: Qing Y
authors.initials: QY
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D019465:Craniofacial Abnormalities / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004432:Ear, Middle / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005786:Gene Expression Regulation; D034381:Hearing Loss / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009092:Mucous Membrane / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D010033:Otitis Media / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D010641:Phenotype; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C533499:Fad49 protein, mouse; D018836:Inflammation Mediators; D049294:Phospholipid Transfer Proteins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha