Biology Reference
In-Depth Information
human genomes can also give clues to genes in the region, which can then
be used for finer mapping, or for investigation as candidate genes for
involvement in the deafness.
Because the sequence of the human genome, and some indication of the
location of coding sequences within it, is likely to be available very soon,
whereas the complete mouse sequence will be at least a couple of years
later, comparisons of human and mouse sequence will be of particular
importance to mouse geneticists over the next few years. There are several
Web sites available that provide valuable information about specific aspects
of genetic deafness, including comparisons of human and mouse deafness
loci (Zheng et al. 2000) and expression of genes in the ear (Bussoli et al.
2000; Morton 2000). Johnson and colleagues also have a useful review of
mouse mutants with ear defects (Johnson et al. 2000). The tables of deaf
mutants presented in this chapter will be updated periodically and be avail-
able at a new Web site (Steel 2000).
There are now many different mouse mutants described in the literature
with auditory-system defects of one sort or another, and more that seem to
be good candidates for involvement in hearing even though they have not
yet been investigated thoroughly. In this chapter, the main types of defects
seen in mouse models, and how these models relate to human deafness, are
discussed. Further details of mouse mutants with specific auditory-system
defects reported in the literature, together with key references, are provided
in the tables.
2. Classifying Defects
It can be argued that, as each mouse mutant involves a mutation in a dif-
ferent gene, and hence represents a unique interference in a specific mole-
cule, there is little point in grouping mutants together according to gross
pathology. However, molecules do not act in isolation, but in the context of
cellular and tissue systems. Thus, mutations may affect different molecules,
but still affect the same functional or developmental system. It will be
important to understand these whole systems, not only to give a complete
understanding of the molecular basis of normal auditory function and
development for academic interest, but also because the prospects for
treatment will be much improved if the whole system is understood.
Because human genetic deafness is highly heterogeneous (many different
genes are involved, any one of which can underlie the deafness in an indi-
vidual), it is likely that the investment needed to develop any treatments
will depend upon generic approaches, which deal with the whole system
rather than a single step. For example, treatments might be developed to
boost the proposed recycling of potassium within the cochlear duct, irre-
spective of which component of the cycle is the weak link. Another example
is stimulation of hair cell regeneration irrespective of the cause of the
