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and normal cochlear response thresholds, but thresholds are raised when
measured from central nuclei, suggesting a defect of central origin (Bock
et al. 1983; Horner and Bock 1985).
Lastly, two mutants show specific central auditory-system dysfunction.
The nociceptin-receptor knock-out mouse shows normal thresholds, but an
impaired ability to recover from intense sound exposure. The expression of
this receptor molecule around the crossed olivocochlear bundle, which sup-
plies the contralateral efferent neurons to the cochlear hair cells, suggests
the receptor may act by modulating efferent activity (Nishi et al. 1997).
Proline dehydrogenase (
Prodh
) mutants also show normal thresholds, but
attenuated pre-pulse inhibition, a phenomenon whereby the behavioural
response to a sound is moderated by prior exposure to a pre-pulse. This
observation suggests a defect in central processes of sensorimotor gating
(Gogos et al. 1999).
It is very likely that many other mouse mutants, particularly those with
generalized neurological defects, will be shown to have specific auditory
system anomalies, but most of them have not yet been analysed in any
detail. Central auditory system anomalies are highly likely to be found in
any cases of peripheral hearing impairment because of the importance of
normal sensory input to refining the neural circuitry of the brain during
development. However, specific central auditory system defects are rela-
tively rare in humans, and there are no clear examples wherein comparison
with any of the mouse models described above is possible. However,
pre-pulse inhibition has been described as a feature of schizophrenia, so
any mouse mutants showing this feature may be of particular interest to
psychiatric research.
3. Summary
There is now a large number of mouse mutants with hearing and/or balance
defects available for investigating the reasons for the impairment, and these
mutants will all contribute to our growing understanding of the com-
plexity of deafness. Many more mouse mutants are candidates for involve-
ment of the auditory system, but their hearing has not yet been investigated
in any detail. Some of these are listed in additional tables available at the
Web site accompanying this chapter (Steel 2000). However, comparison of
the chromosomal locations of these mutations causing deafness in the
mouse with the locations of known human deafness mutations reveals that
there are many human loci for which no mouse model has yet been dis-
covered. Two major mutagenesis programs are ongoing in Europe, at
Neuherberg, Germany and Harwell, UK, and new deaf mouse mutants are
being isolated from these screens to help to fill the gap between human
deafness and mouse models (Nolan et al. 2000). Large-scale, genome-wide
mutagenesis programmes are starting in other countries too, including the
