title: A novel model of spontaneous otitis media with effusion (OME) in the Oxgr1 knock-out mouse.
abstract: OBJECTIVE
  A novel mouse model with a specific genetic mutation in a G protein coupled receptor (GPCR) encoded by the Oxgr1 gene results in a predisposition to spontaneous otitis media with effusion. As a primary component of interest in OME, mucin expression was examined in this model to assess expression as compared to wild type animals and suitability as a murine model of OME.
  
  
  METHODS
  Mutant (Oxgr1(-/-)) and wild-type (Oxgr1(+/+)) mice between ages of 2 and 5 months were examined by otoscopy and auditory brainstem response (ABR). Histology changes in the middle ear were evaluated. Expression of mucin genes in the middle ear epithelium was determined using RT-PCR and quantitative PCR.
  
  
  RESULTS
  Otoscopic exam showed signs of inflammation in 82% of mutant mice. Significant elevated ABR thresholds were detected in mutant mice indicating hearing loss. Histology analysis of the middle ears demonstrated the presence of inflammatory cells, changes in the mucosal epithelium, and middle ear fluid. RT PCR using universal primers for bacterial 18s rRNA suggested the absence of bacteria in the middle ear. The knockout mice demonstrated expression of Muc1, Muc2, Muc3, Muc4, Muc5AC, Muc5B, Muc9, Muc10, Muc13, Muc15, Muc16, Muc18, Muc19 and Muc20. There was a trend of increase in Muc5B and Muc19 expression in the middle ear of the knockout mice compared to that of wild-type. There was no significant change in the level of Muc2, and Muc5AC was expressed at a level below the detection limit of quantification.
  
  
  CONCLUSIONS
  Development of a murine model with genetic defect has several attractive features. The rate of OME in these animals is high at 82%. It is clear that this OME is related to histopathologic changes in the middle ear epithelium of these knock-out mice. Induction of mucus effusion is evident though the viation in dysregulation of GFM does exist in this non-challenge study condition. The underlying cause of these differences between individual animal requires further investigation. Given this, the Oxgr1(-/-) model is likely to be an ideal model to examine mucin regulation in MEE and potentially develop novel GPCR-specific targeted interventions to regulate these processes.
authors.affiliation: Division of Pediatric Otolaryngology, 9000 West Wisconsin Avenue, Milwaukee, WI 53226, United States. kersch@mcw.edu
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Kerschner
authors.forename: Wenzhou
authors.initials: W
authors.lastname: Hong
authors.forename: Steven R
authors.initials: SR
authors.lastname: Taylor
authors.forename: John A
authors.initials: JA
authors.lastname: Kerschner
authors.forename: Pawjai
authors.initials: P
authors.lastname: Khampang
authors.forename: Kay C
authors.initials: KC
authors.lastname: Wrege
authors.forename: Paula E
authors.initials: PE
authors.lastname: North
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem; D005786:Gene Expression Regulation; D005838:Genotype; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009077:Mucins / Q000235:genetics* / Q000378:metabolism; D010034:Otitis Media with Effusion / Q000235:genetics* / Q000473:pathology; D038781:Otoscopy / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D009077:Mucins; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; C486887:OXGR1 protein, mouse