Biology Reference
In-Depth Information
1999). In these mutants, ultrastructural study of the spiral ligament fibro-
cytes revealed that they had a reduction in the extent of cell-to-cell con-
nections, and this was associated with a reduced EP measured in scala
media. One possible explanation for these findings is that reduced connec-
tions between fibrocytes lowered the amount of potassium that could be
passed through, in turn affecting the production of the EP by the stria. The
POU3F4
gene is mutated in human X-linked mixed deafness, but it is dif-
ficult to imagine that EP could ever be recorded in humans. Thus, making
a direct comparison of the cochlear pathology in the two species is difficult.
However, a reduced EP could explain the sensorineural component of the
mixed hearing impairment observed in these people.
Gap junctions lead up to the basal cells of the stria vascularis. Here, the
abundant Na
+
,K
+
ATPase is believed to act in concert with a Na
+
,K
+
, 2Cl
-
co-transporter to transport potassium into the marginal cells lining the
lumenal surface of the cochlear duct. In the
shaker-with-syndactylism
mouse mutant, as well as two knockout mutations of the
Slc12a2
gene,
the endolymphatic compartments collapse at around the time of birth,
suggesting that it is indeed the co-transporter encoded by this gene that
is involved in potassium pumping into marginal cells (Dixon et al. 1999;
Delpire et al. 1999; Flagella et al. 1999). Once inside the marginal cell,
potassium is thought to pass down its electrochemical gradient into the
endolymph via a potassium channel on the lumenal surface formed from
the products of two genes,
KCNQ1
and
KCNE1
. Either of these genes can
be mutated in human Jervell and Lange-Neilsen syndrome (Griffith and
Friedman, Chapter 6). Mutations of the mouse orthologues show early
collapse of the endolymphatic compartments, supporting the suggestion
that these genes are essential for endolymph production (Vetter et al. 1996;
Francis et al. 2000). Once in the endolymph, the potassium is available once
more for the transduction current into hair cells.
Melanocytes form an essential component of the stria vascularis. The
intermediate cells are specialized melanocytes that are scattered between
the marginal cells on the lumenal side (derived from the otic epithelium),
and the basal cells (derived from the mesenchyme). Melanocytes originate
in the neural crest during early development, and migrate to the inner ear
to ultimately populate the stria vascularis as well as specific locations in the
vestibular part of the ear (Steel and Barkway 1989; Steel et al. 1992; Cable
et al. 1995). The melanocytes extend many cellular processes that inter-
digitate with adjacent marginal and basal cell processes. In the young stria
they look like typical melanocytes, with extensive dendrites and many
pigment-laden melanosomes (Cable and Steel 1991). No particular role for
the melanocytes was imagined until the finding that, in mice with no
melanocytes in their strias, no EP was generated (Steel et al. 1987). Several
mouse mutants are now known to have such a defect, including dominant
spotting (
Kit
), steel (
Mgf
), microphthalmia (
Mitf
), piebald (
Ednrb
) and
lethal spotting (
Edn3
), and other mutants with white-spotted coats are
