Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis.
[harlequin ichthyosis]
Harlequin
Ichthyosis
(
HI
)
is
a
severe
and
often
lethal
hyperkeratotic
skin
disease
caused
by
mutations
in
the
ABCA
12
transport
protein
.
In
keratinocytes
,
ABCA
12
is
thought
to
regulate
the
transfer
of
lipids
into
small
intracellular
trafficking
vesicles
known
as
lamellar
bodies
.
However
,
the
nature
and
scope
of
this
regulation
remains
unclear
.
As
part
of
an
original
recessive
mouse
ENU
mutagenesis
screen
,
we
have
identified
and
characterised
an
animal
model
of
HI
and
showed
that
it
displays
many
of
the
hallmarks
of
the
disease
including
hyperkeratosis
,
loss
of
barrier
function
,
and
defects
in
lipid
homeostasis
.
We
have
used
this
model
to
follow
disease
progression
in
utero
and
present
evidence
that
loss
of
Abca
12
function
leads
to
premature
differentiation
of
basal
keratinocytes
.
A
comprehensive
analysis
of
lipid
levels
in
mutant
epidermis
demonstrated
profound
defects
in
lipid
homeostasis
,
illustrating
for
the
first
time
the
extent
to
which
Abca
12
plays
a
pivotal
role
in
maintaining
lipid
balance
in
the
skin
.
To
further
investigate
the
scope
of
Abca
12
's
activity
,
we
have
utilised
cells
from
the
mutant
mouse
to
ascribe
direct
transport
functions
to
the
protein
and
,
in
doing
so
,
we
demonstrate
activities
independent
of
its
role
in
lamellar
body
function
.
These
cells
have
severely
impaired
lipid
efflux
leading
to
intracellular
accumulation
of
neutral
lipids
.
Furthermore
,
we
identify
Abca
12
as
a
mediator
of
Abca
1
-
regulated
cellular
cholesterol
efflux
,
a
finding
that
may
have
significant
implications
for
other
diseases
of
lipid
metabolism
and
homeostasis
,
including
atherosclerosis
.
Diseases
Validation
Diseases presenting
"skin disease"
symptom
child syndrome
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
harlequin ichthyosis
junctional epidermolysis bullosa
kindler syndrome
lamellar ichthyosis
omenn syndrome
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom