Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Methylome repatterning in a mouse model of Maternal PKU Syndrome.
[phenylketonuria]
Maternal
PKU
Syndrome
(
MPKU
)
is
an
embryopathy
resulting
from
in
utero
phenylalanine
(
PHE
)
toxicity
secondary
to
maternal
phenylalanine
hydroxylase
deficient
phenylketonuria
(
PKU
)
.
Clinical
phenotypes
in
MPKU
include
mental
retardation
,
microcephaly
,
in
utero
growth
restriction
,
and
congenital
heart
defects
.
Numerous
in
utero
toxic
exposures
alter
DNA
methylation
in
the
fetus
.
The
PAH
(
enu
2
)
mouse
is
a
model
of
classical
PKU
while
offspring
born
of
hyperphenylalaninemic
dams
model
MPKU
.
We
investigated
offspring
of
PAH
(
enu
2
)
dams
to
determine
if
altered
patterns
of
DNA
methylation
occurred
in
response
to
in
utero
PHE
exposure
.
As
neurologic
deficit
is
the
most
prominent
MPKU
phenotype
,
methylome
patterns
were
assessed
in
brain
tissue
using
methylated
DNA
immunoprecipitation
and
paired-end
sequencing
.
Brain
tissues
were
assessed
in
E
18
.
5
-
19
fetuses
of
PHE
unrestricted
PAH
(
enu
2
)
dams
,
PHE
restricted
PAH
(
enu
2
)
dams
,
and
heterozygous
(
wt
/
enu
2
)
control
dams
.
Extensive
methylome
repatterning
was
observed
in
offspring
of
hyperphenylalaninemic
dams
while
the
offspring
of
PHE
restricted
dams
displayed
attenuated
methylome
repatterning
.
Methylation
within
coding
regions
was
dominated
by
noncoding
RNA
genes
.
Differential
methylation
of
promoters
targeted
protein
coding
genes
.
To
assess
the
impact
of
methylome
repatterning
on
gene
expression
,
brain
tissue
in
experimental
and
control
animals
were
queried
with
microarrays
assessing
expression
of
microRNAs
and
protein
coding
genes
.
Altered
expression
of
methylome-modified
microRNAs
and
protein
coding
genes
was
extensive
in
offspring
of
hyperphenylalaninemic
dams
while
minimal
changes
were
observed
in
offspring
of
PHE
restricted
dams
.
Several
genes
displaying
significantly
reduced
expression
have
roles
in
neurological
function
or
genetic
disease
with
neurological
phenotypes
.
These
data
indicate
in
utero
PHE
toxicity
alters
DNA
methylation
in
the
brain
which
has
downstream
impact
upon
gene
expression
.
Altered
gene
expression
may
contribute
to
pathophysiology
of
neurologic
presentation
in
MPKU
.
Diseases
Validation
Diseases presenting
"restricted dams"
symptom
phenylketonuria
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom