Rare Diseases Symptoms Automatic Extraction
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GFAP expression as an indicator of disease severity in mouse models of Alexander disease.
[alexander disease]
AxD
(
Alexander
disease
)
is
a
rare
disorder
caused
by
heterozygous
mutations
in
GFAP
(
glial
fibrillary
acidic
protein
)
resulting
in
accumulation
of
the
GFAP
protein
and
elevation
of
Gfap
mRNA
.
To
test
whether
GFAP
itself
can
serve
as
a
biomarker
of
disease
status
or
progression
,
we
investigated
two
independent
measures
of
GFAP
expression
in
AxD
mouse
models
,
one
using
a
genetic
reporter
of
promoter
activity
and
the
other
quantifying
GFAP
protein
directly
in
a
manner
that
could
also
be
employed
in
human
studies
.
Using
a
transgenic
reporter
line
that
expresses
firefly
luciferase
under
the
control
of
the
murine
Gfap
promoter
(
Gfap-luc
)
,
we
found
that
luciferase
activity
reflected
the
regional
CNS
(
central
nervous
system
)
variability
of
Gfap
mRNA
in
Gfap
(
+
/
+
)
mice
,
and
increased
in
mice
containing
a
point
mutation
in
Gfap
that
mimics
a
common
human
mutation
in
AxD
(
R
239
H
in
the
human
sequence
,
and
R
236
H
in
the
murine
sequence
)
.
In
a
second
set
of
studies
,
we
quantified
GFAP
protein
in
CSF
(
cerebrospinal
fluid
)
taken
from
three
different
AxD
mouse
models
and
littermate
controls
.
GFAP
levels
in
CSF
were
increased
in
all
three
AxD
models
,
in
a
manner
corresponding
to
the
concentrations
of
GFAP
in
brain
.
These
studies
demonstrate
that
transactivation
of
the
Gfap
promoter
is
an
early
and
sustained
indicator
of
the
disease
process
in
the
mouse
.
Furthermore
,
GFAP
in
CSF
serves
as
a
potential
biomarker
that
is
comparable
between
mouse
models
and
human
patients
.
