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Liver aging and pseudocapillarization in a Werner syndrome mouse model.
[werner syndrome]
Werner
syndrome
is
a
progeric
syndrome
characterized
by
premature
atherosclerosis
,
diabetes
,
cancer
,
and
death
in
humans
.
The
knockout
mouse
model
created
by
deletion
of
the
RecQ
helicase
domain
of
the
mouse
Wrn
homologue
gene
(
Wrn
(
∆
hel
/
∆
hel
)
)
is
of
great
interest
because
it
develops
atherosclerosis
and
hypertriglyceridemia
,
conditions
associated
with
aging
liver
and
sinusoidal
changes
.
Here
,
we
show
that
Wrn
(
∆
hel
/
∆
hel
)
mice
exhibit
increased
extracellular
matrix
,
defenestration
,
decreased
fenestration
diameter
,
and
changes
in
markers
of
liver
sinusoidal
endothelial
cell
inflammation
,
consistent
with
age-related
pseudocapilliarization
.
In
addition
,
hepatocytes
are
larger
,
have
increased
lipofuscin
deposition
,
more
frequent
nuclear
morphological
anomalies
,
decreased
mitochondria
number
,
and
increased
mitochondrial
diameter
compared
to
wild-
type
mice
.
The
Wrn
(
∆
hel
/
∆
hel
)
mice
also
have
altered
mitochondrial
function
and
altered
nuclei
.
Microarray
data
revealed
that
the
Wrn
(
∆
hel
/
∆
hel
)
genotype
does
not
affect
the
expression
of
many
genes
within
the
isolated
hepatocytes
or
liver
sinusoidal
endothelial
cells
.
This
study
reveals
that
Wrn
(
∆
hel
/
∆
hel
)
mice
have
accelerated
typical
age-related
liver
changes
including
pseudocapillarization
.
This
confirms
that
pseudocapillarization
of
the
liver
sinusoid
is
a
consistent
feature
of
various
aging
models
.
Moreover
,
it
implies
that
DNA
repair
may
be
implicated
in
normal
aging
changes
in
the
liver
.
Diseases
Validation
Diseases presenting
"cancer"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated