Faculty Collaboration Database

A novel model of spontaneous otitis media with effusion (OME) in the Oxgr1 knock-out mouse. Int J Pediatr Otorhinolaryngol 2013 Jan;77(1):79-84

Date

12/04/2012

Pubmed ID

23200873

Pubmed Central ID

PMC3535456

DOI

10.1016/j.ijporl.2012.09.037

Scopus ID

2-s2.0-84871494595 (requires institutional sign-in at Scopus site)   24 Citations

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.

METHOD: 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.

RESULT: 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.

CONCLUSION: 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.

Author List

Kerschner JE, Hong W, Taylor SR, Kerschner JA, Khampang P, Wrege KC, North PE

Authors

Wenzhou Hong DVM, PhD Assistant Professor in the Otolaryngology department at Medical College of Wisconsin
Joseph E. Kerschner MD Provost, Executive Vice President, Dean, Professor in the School of Medicine Administration department at Medical College of Wisconsin
Paula E. North MD, PhD Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Biopsy, Needle
Disease Models, Animal
Evoked Potentials, Auditory, Brain Stem
Gene Expression Regulation
Genotype
Immunohistochemistry
Mice
Mice, Inbred C57BL
Mice, Knockout
Mucins
Otitis Media with Effusion
Otoscopy
RNA, Messenger
Random Allocation
Receptors, Purinergic P2
Reverse Transcriptase Polymerase Chain Reaction