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Protein changes in immunodepleted cerebrospinal fluid from a transgenic mouse model of Alexander disease detected using mass spectrometry.
[alexander disease]
Cerebrospinal
fluid
(
CSF
)
is
a
low
protein
content
biological
fluid
with
a
dynamic
range
spanning
at
least
9
orders
of
magnitude
in
protein
content
and
is
in
direct
contact
with
the
brain
.
A
modified
IgY-
14
immunodepletion
treatment
was
performed
to
enhance
analysis
of
the
low
volumes
of
CSF
that
are
obtainable
from
mice
.
As
a
model
system
in
which
to
test
this
approach
,
we
utilized
transgenic
mice
that
overexpress
the
intermediate
filament
glial
fibrillary
acidic
protein
(
GFAP
)
.
These
mice
are
models
for
Alexander
disease
(
AxD
)
,
a
severe
leukodystrophy
in
humans
.
From
the
CSF
of
control
and
transgenic
mice
we
report
the
identification
of
289
proteins
,
with
relative
quantification
of
103
proteins
.
Biological
and
technical
triplicates
were
performed
to
address
animal
variability
as
well
as
reproducibility
in
mass
spectrometric
analysis
.
Relative
quantitation
was
performed
using
distributive
normalized
spectral
abundance
factor
(
dNSAF
)
spectral
counting
analysis
.
A
panel
of
biomarker
proteins
with
significant
changes
in
the
CSF
of
GFAP
transgenic
mice
has
been
identified
with
validation
from
enzyme-linked
immunosorbent
assay
(
ELISA
)
and
microarray
data
,
demonstrating
the
utility
of
our
methodology
and
providing
interesting
targets
for
future
investigations
on
the
molecular
and
pathological
aspects
of
AxD
.
Diseases
Validation
Diseases presenting
"low protein content"
symptom
alexander disease
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