Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
An N-ethyl-N-nitrosourea induced corticotropin-releasing hormone promoter mutation provides a mouse model for endogenous glucocorticoid excess.
[cushing syndrome]
Cushing
's
syndrome
,
which
is
characterized
by
excessive
circulating
glucocorticoid
concentrations
,
may
be
due
to
ACTH-dependent
or
-
independent
causes
that
include
anterior
pituitary
and
adrenal
cortical
tumors
,
respectively
.
ACTH
secretion
is
stimulated
by
CRH
,
and
we
report
a
mouse
model
for
Cushing
's
syndrome
due
to
an
N-
ethyl-
N-
nitrosourea
(
ENU
)
induced
Crh
mutation
at
-
120
bp
of
the
promoter
region
,
which
significantly
increased
luciferase
reporter
activity
and
was
thus
a
gain-of-function
mutation
.
Crh
(
-
120
/
+
)
mice
,
when
compared
with
wild-
type
littermates
,
had
obesity
,
muscle
wasting
,
thin
skin
,
hair
loss
,
and
elevated
plasma
and
urinary
concentrations
of
corticosterone
.
In
addition
,
Crh
(
-
120
/
+
)
mice
had
hyperglycemia
,
hyperfructosaminemia
,
hyperinsulinemia
,
hypercholesterolemia
,
hypertriglyceridemia
,
and
hyperleptinemia
but
normal
adiponectin
.
Crh
(
-
120
/
+
)
mice
also
had
low
bone
mineral
density
,
hypercalcemia
,
hypercalciuria
,
and
decreased
concentrations
of
plasma
PTH
and
osteocalcin
.
Bone
histomorphometry
revealed
Crh
(
-
120
/
+
)
mice
to
have
significant
reductions
in
mineralizing
surface
area
,
mineral
apposition
,
bone
formation
rates
,
osteoblast
number
,
and
the
percentage
of
corticoendosteal
bone
covered
by
osteoblasts
,
which
was
accompanied
by
an
increase
in
adipocytes
in
the
bone
marrow
.
Thus
,
a
mouse
model
for
Cushing
's
syndrome
has
been
established
,
and
this
will
help
in
further
elucidating
the
pathophysiological
effects
of
glucocorticoid
excess
and
in
evaluating
treatments
for
corticosteroid-induced
osteoporosis
.
Diseases
Validation
Diseases presenting
"hypercalcemia"
symptom
carcinoma of the gallbladder
cushing syndrome
familial hypocalciuric hypercalcemia
kabuki syndrome
severe combined immunodeficiency
waldenström macroglobulinemia
This symptom has already been validated