Mice as Models for Human Hereditary Deafness - Genetics of Auditory Disorders - page 267

FIGURE 8.4. A schematic representation of the cochlear duct showing the expres-
sion pattern of genes thought to be involved in recycling of potassium. KCNQ4 is
expressed in the hair cells. GJB2 , GJB3 and GJB6 are expressed in the supporting
cells of the organ of Corti and in the fibrocytes of the spiral ligament. Pou3f4 is
expressed in the spiral ligament. Kit , Mgf , Mitf , Edn3 and Ednrb are all involved in
the migration of melanoblasts from the neural crest to the stria and their later dif-
ferentiation into melanocytes, although these genes are not necessarily expressed in
the mature melanocytes. In the marginal cells of the stria vascularis, Slc12a2 encodes
a Na-K-Cl co-transporter located on the basolateral membranes, while KVLQT1
( KCNQ1 ) and IsK ( KCNE1) are channel proteins located at the lumenal surface
of the marginal cells. See text for further details.
(Fig. 8.4). Potassium is known to flood into the hair cell when it is stimu-
lated by sound, and it needs to be removed. KCNQ4 encodes a potassium
channel expressed in cochlear hair cells, and has been proposed as a route
for the removal of potassium from these cells. Mutation of KCNQ4 leads
to dominantly inherited, progressive hearing loss in humans, but no mouse
model has yet been reported (Kubisch et al. 1999). Next, the potassium is
thought to be taken up by supporting cells and passed through gap junc-
tions to the spiral ligament (laterally), or the spiral limbus (medially). Muta-
tions in three human connexin genes ( GJB2 , GJB3 and GJB6 ) expressed
in the cochlear duct cause hearing impairment in humans (Denoyelle et al.
1998; Grifa et al. 1999; Kelsell et al. 1997; Xia et al. 1998; Liu et al. 2000),
but again no mouse mutants have yet been reported. Evidence that the
spiral ligament is important in supporting the generation of the EP comes
from a mouse mutant with the Pou3f4 gene inactivated (Minowa et al.