Michael D. McGinn

Cholesteatoma: Experimental Induction in the Mongolian Gerbil, Meriones Unguiculaus

Surgical ligation of the external auditory canal of the Mongolian gerbil produces aural cholesteatomas that are similar to the spontaneous gerbilline cholesteatoma. Some 6-9 months after ligation of the external auditory canal, these cholesteatomas are in contact with the bone of the middle ear. These induced cholesteatomas were seen to erode bone and displace soft tissue structures, as is typical of human aural cholesteatomas. The induced gerbilline cholesteatoma is an ideal experimental model for the study of the osteolytic characteristics of cholesteatoma.

Auditory experience affects degeneration of the ventral cochlear nucleus in mongolian gerbils

Gerbils exhibit a unique encephalopathy characterized by spongioform lesions in the neuropil of the cochlear nucleus and that others have recently described. The present results suggest that the course of this degenerative disorder is affected by acoustic experience. In gerbils in which acoustic stimulation was limited postnatally, the number and the extent of these lesions was dramatically reduced. Monaural deprivation reduced lesion number and extent only in the ipsilateral cochlear nucleus; binaural deprivation affected both cochlear nuclei. The lesions were most evident in certain portions of the cochlear nucleus, the caudal anterior ventral cochlear nucleus and the posterior ventral cochlear nucleus, sparing the rostral pole of the anterior ventral cochlear nucleus. In the affected regions the lesions were topologically restricted to the low and middle frequency regions. The apparent tonotopic distribution of lesions was associated with frequent exposure to low and middle frequency ambient noise.

Age-related auditory loss in the Mongolian gerbil

SummaryMongolian gerbils were examined for auditory nerve function at five ages, ranging from 90 to 730 days postpartum. Electrocochleograms were obtained in response to tone pips at frequencies ranging from 1 to 64 kHz. An age-related threshold increase was noted at all frequencies. The pattern of auditory loss is different from that observed in the aged rat, guinea pig, and mouse.

The mouse as a model for human audition. A review of the literature.

The mouse has several distinct advantages as an experimental model for human audition. Mice and humans express a similar presbyacusic and ototraumatic pattern. Several genetic mouse models also exist for conditions resembling human auditory disorders, such as otosclerosis. This paper reviews the strains of inbred mice (e.g. the CBA/J) which have recently been used as models for the normal human auditory system, describing their deficiencies. It is suggested that the F1 offspring of CBA/CaJ and AU/SsJ inbred mice would have advantages over existing models.

Incidence of otitis media in CBA/J and CBA/CaJ mice.

The inbred CBA/J mouse has become a standard experimental animal for auditory study because of its lifelong good hearing. In a newly established mouse breeding colony that housed CBA/J and CBA/CaJ mice to reared as auditory subjects, otitis media frequently afflicted CBA/J mice, reaching an incidence of 90% in animals greater than 400 days of age. Otitis media was not found in CBA/CaJ mice. Three attempts to establish a colony that was free of otitis were unsuccessful. Although the primary pathogen was not clearly established, Pasteurella pneumotropica was isolated from infected bullae. Partial control of otitis media followed the introduction of tetracycline prophylaxis. The CBA/CaJ mice may be suitable replacements for CBA/J mice in studies that require inbred mice with good hearing, since their auditory thresholds did not differ significantly from those of otitis-free CBA/J mice.

Cholesteatoma Induction:Consequences of External Auditory Canal Ligation in Gerbils, Cats, Hamsters, Guinea Pigs, Mice and Rats

Surgical ligation of the external auditory canals of Mongolian gerbils produces aural cholesteatomas that are similar to spontaneous gerbilline cholesteatomas. These experimental cholesteatomas expand rapidly, medially displacing the tympanic membrane and eroding bone. Less than 2 months after ligation, half these cholesteatomas are in contact with the bony prominence of the cochlea. Ligation-induced formation of cholesteatomas may be unique to the gerbil. Keratin deposits are produced by similar ligations of the external auditory canals of cats, guinea pigs, hamsters, mice, and rats. However, in these animals there is no medial displacement of the tympanic membrane, no cholesteatoma formation, and no bone erosion. Cholesteatomas were not seen in cats, guinea pigs, hamsters, mice, and rats even after post-ligation intervals of 6 to 36 months.

Inhibition of nitric oxide synthase blocks osteoclastic bone resorption in adaptive bone modeling

In this study, the auditory bulla of the gerbil was pressurized, leading to active modeling of the bone of the bulla wall with a significant increase in osteoclast surface and mineral apposition rate. Systemic infusion of L-N(G)-nitro-arginine-methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), inhibited this modeling process. The percentage osteoclast surface (Oc.S/BS) on the inner surface bulla wall was significantly reduced in the L-NAME-treated animals when compared with pressurized saline-treated bullae. Fluorescent bone surface (BSf) mineral apposition rates (MAR) and bone formation rate (BFR) were not significantly different in the pressurized bullae when the L-NAME group was compared with the control (vehicle only) group. However, L-NAME significantly suppressed BSf in the unpressurized bullae. Therefore, it is likely that nitric oxide is a mediator of osteoclastic resorption due to adaptive bone modeling through one or more of the isoforms of NOS.

Glial Populations in the Juvenile and Adult Mongolian Gerbil: Relationship to Spongiform Degeneration of the Ventral Cochlear Nucleus

The gerbil cochlear nucleus is subject to a spongiform degeneration, the progression of which is dependent on auditory functional activity. The most affected region is the ventrolateral aspect of the caudal posterior ventral cochlear nucleus (PVCN). Lesion density and glial changes were quantified in this region for two age groups. Spongiform lesions increased significantly in area density from 4% in 60-day-old gerbils to 14% in 6-month-old gerbils. In spite of this significant increase in tissue damage, no gliosis was found. A significant age-related decrease in oligodendrocyte density was found in the PVCN.

Neuronal degeneration in the gerbil brainstem is associated with spongiform lesions

Spongiform lesions arise in dendrites and glia in the brainstem of domestic Mongolian gerbils. Most pronounced within the cochlear nucleus (CN), this disorder is dynamic and progressive; the lesions increase in number, size, and extent with age. It has not been clear whether these spongioid lesions either cause or are associated with significant neural degeneration. In contrast, feral Mongolian gerbils (wild‐trapped in Tuva) and their offspring show few spongiform lesions. The Tuvan gerbils provide an appropriate within‐species control.

Auditory Brainstem Function of the F1 Offspring of the Cross of CBA/CaJ and AU/SsJ Inbred Mice

Inbred strains of laboratory mice have several distinct advantages as models for examining conditions that influence the human auditory system, but the CBA/J mouse which has most often been used as a normal model has recently been found to have several disadvantages. This paper is the first report of the auditory brainstem responses (ABRs) of the F1 offspring of CBA/CaJ and AU/SsJ parents. At midlife, high-frequency ABR thresholds are lower in the F1 than in either parental genotype. Tuning curves obtained by forward masking of the ABR also display heterosis, i.e. they are narrower in the F1 than in either parental strain.