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Sporadic obstructive hydrocephalus in Aqp4 null mice.
[hydrocephalus with stenosis of the aqueduct of sylvius]
Aquaporin-
4
(
Aqp
4
)
is
a
water
transport
protein
expressed
in
glia
and
ependymocytes
in
brain
.
We
report
here
the
unexpected
occurrence
of
severe
obstructive
hydrocephalus
in
a
random
subset
of
Aqp
4
knockout
mice
.
Of
612
Aqp
4
knockout
mice
produced
by
heterozygote-heterozygote
or
knockout-knockout
breedings
,
9
.
6
%
of
offspring
manifested
progressive
encephalomegaly
.
Encephalomegaly
was
never
seen
in
wild-
type
or
Aqp
4
heterozygous
mice
.
Examination
of
the
subset
encephalomegalic
mice
revealed
marked
triventricular
hydrocephalus
(
lateral
ventricle
size
approximately
500
mm
(
3
)
)
,
elevated
intracranial
pressure
(
19
+
/
-
3
vs
.
6
.
1
+
/
-
0
.
6
mm
Hg
)
,
and
death
by
age
6
weeks
,
with
a
median
survival
of
28
days
.
Intraventricular
dye
injection
studies
revealed
total
obstruction
of
the
cerebral
aqueduct
.
Evans
blue
extravasation
studies
indicated
an
intact
blood
-
brain
barrier
in
the
hydrocephalic
mice
.
Brain
histology
revealed
reduced
ventricular
size
and
ependymocyte
disorganization
in
some
nonhydrocephalic
Aqp
4
null
mice
.
Our
studies
establish
Aqp
4
deletion
as
a
predisposing
factor
for
the
development
of
congenital
obstructive
hydrocephalus
in
mice
.
We
suggest
that
AQP
4
polymorphisms
might
also
contribute
to
the
development
of
aqueduct
stenosis
in
humans
.
Diseases
Validation
Diseases presenting
"reduced ventricular size and ependymocyte disorganization"
symptom
hydrocephalus with stenosis of the aqueduct of sylvius
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