Biology Reference
In-Depth Information
which provides information to the brain about head movement. Otolithic
membranes lie over the saccular and utricular maculae. They contain small,
calcium-rich, crystalline structures called otoliths, which make the otolithic
membrane denser than the surrounding endolymph. The gravitational force
on the otoliths provides information to the brain about head position. These
extracellular membranes are secreted by the underlying epithelium, most
likely by the supporting cells.
Several of the mutants described have abnormal otolithic membranes,
either small or undetectable, or containing giant otoliths. The defects
can be variable among mutants, and can be unilateral (Lim et al. 1978;
Trune and Lim 1983a,b). The genes so far identified encode calcium chan-
nels and pumps (
Slc30a4
;
Atp2b2
), a component of the intracellular secre-
tory pathway (
Ap3d
), and an extracellular matrix molecule (
Otog
) that
appears to be required to attach the membrane to the underlying epithe-
lium. Defective otolithic membranes have been described in mutations of
two transcription factors (
Atf2
and
Msx2
). Such defects may be secondary
to gross inner ear malformations, and there are probably many examples
of inner ear malformations with otolithic or cupular defects that are not
specifically described in the literature. Mutants with specific otolithic or
cupular membrane defects do not necessarily have impaired cochlear func-
tion, and no humans with mutations in the same genes have been described
yet.
The tectorial membrane is the extracellular matrix of the cochlea, and is
secreted by the supporting cells of the organ of Corti as well as the cells of Köl-
liker's organ during development. Kölliker's organ later regresses to form the
inner spiral sulcus. Abnormalities of the tectorial membrane have been
described in many different deaf mouse mutants. However, the structure is
notoriously susceptible to histological artefact during preparation, and when
underlying hair cells degenerate, it loses some of its attachment points, so care
must be taken in interpreting these observations, since they may not involve
a primary tectorial membrane defect. However, recently four different
mutants have been described that do seem likely to involve primary tectorial
membrane defects and associated hearing impairment. The
Col11a2
knock-
out and the
Otog
knock-out mutations have both been described with subtle
ultrastructural anomalies of the tectorial membrane, suggesting that the mol-
ecules encoded by these genes are probably components of this membrane
(Simmler et al. 2000; McGuirt et al. 1999). A targetted mutation of
Tecta
,in
contrast, leads to major ultrastructural abnormalities of the tectorial mem-
brane, which is not surprising because the a-tectorin molecule encoded by
Tecta
was identified previously as a major component of the membrane
(Legan et al. 2000). Lastly, double mutants for two thyroid hormone recep-
tors,
Thra
and
Thrb
, show more severely elevated thresholds than the
Thrb
-
deficient single mutant, and preliminary analysis indicates the presence of
some malformation of the tectorial membrane in the double mutant (M
Kelley and D Forrest, personal communication 2000).
