C3H/HeJ Mouse Model for Spontaneous Chronic Otitis Media

Abstract

The histopathologic changes reported here in the C3H/HeJ mouse model of chronic otitis media have been reported in human chronic otitis media. This spontaneous model of chronic otitis media will be valuable for the characterization of middle and inner ear inflammatory disease processes that are induced by middle ear infections.

Evaluation of the mouse model for acute otitis media

“…Our laboratories are currently investigating the use of intracellular inflammatory inhibitors to suppress OM in the mouse model (McCoy et al, 2005). Also, genetic variants in toll-like receptors are proving valuable in ongoing studies of chronic OM and its effect on the inner ear (Mitchell et al, 1997;MacArthur et al, 2006). This model will continue to be a useful tool in many aspects of OM research, although its experimental limitations must be clearly defined.…”

“…The mouse is small, inexpensive to buy and house, and easy to handle, making it an attractive animal model. The mouse also offers the researcher the availability of advanced molecular reagents, numerous transgenic and gene deletion strains, as well as many genetic models such as craniofacial (Hardisty et al, 2003) and immune system variants for chronic OM studies (MacArthur et al, 2006;Mitchell et al, 1997). Although the small middle ear of the mouse is technically more difficult to access and manipulate than larger animal models, use of the surgical microscope and small needles allow the researcher to experimentally adjust to the small TM.…”

Tympanometry assessment of 61 inbred strains of mice

“…A survey of the literature shows that older 129S6 mice (not tested here) showed middle ear disease after a year (Rosowski et al, 2003), much older than the mice studied here in some strains. Further, C3H/HeJ mice develop consistent middle ear disease because of a compromised TLR4 receptor (MacArthur et al, 2006), but the majority develop middle ear disease after six months. In our study, the oldest C3H/ HeJ mice tested were 6-month-old; hence, our tympanometry results yielded normal parameters for this strain.…”

Eya4-deficient mice are a model for heritable otitis media

“…These mice indicate several distinct mechanisms by which otitis media vulnerability can be increased. A missense mutation in the TLR4 gene renders C3H/HeJ mice unresponsive to LPS and vulnerable to Gram-negative organisms, including H. influenzae, one of the common bacterial causes of human otitis media (41). Evi1-null mice, produced during a N-ethyl-N-nitrosourea mutagenesis screen, exhibited increased susceptibility to otitis media, possibly by affecting transcriptional regulation of neutrophil or mucin genes through a TGF-β/SMAD signaling pathway (42).…”