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Transcriptional repression of the Dspp gene leads to dentinogenesis imperfecta phenotype in Col1a1-Trps1 transgenic mice.
[dentinogenesis imperfecta]
Dentinogenesis
imperfecta
(
DGI
)
is
a
hereditary
defect
of
dentin
,
a
calcified
tissue
that
is
the
most
abundant
component
of
teeth
.
Most
commonly
,
DGI
is
manifested
as
a
part
of
osteogenesis
imperfecta
(
OI
)
or
the
phenotype
is
restricted
to
dental
findings
only
.
In
the
latter
case
,
DGI
is
caused
by
mutations
in
the
DSPP
gene
,
which
codes
for
dentin
sialoprotein
(
DSP
)
and
dentin
phosphoprotein
(
DPP
)
.
Although
these
two
proteins
together
constitute
the
majority
of
noncollagenous
proteins
of
the
dentin
,
little
is
known
about
their
transcriptional
regulation
.
Here
we
demonstrate
that
mice
overexpressing
the
Trps
1
transcription
factor
(
Col
1
a
1
-
Trps
1
mice
)
in
dentin-producing
cells
,
odontoblasts
,
present
with
severe
defects
of
dentin
formation
that
resemble
DGI
.
Combined
micro-computed
tomography
(
µCT
)
and
histological
analyses
revealed
tooth
fragility
due
to
severe
hypomineralization
of
dentin
and
a
diminished
dentin
layer
with
irregular
mineralization
in
Col
1
a
1
-
Trps
1
mice
.
Biochemical
analyses
of
noncollagenous
dentin
matrix
proteins
demonstrated
decreased
levels
of
both
DSP
and
DPP
proteins
in
Col
1
a
1
-
Trps
1
mice
.
On
the
molecular
level
,
we
demonstrated
that
sustained
high
levels
of
Trps
1
in
odontoblasts
lead
to
dramatic
decrease
of
Dspp
expression
as
a
result
of
direct
inhibition
of
the
Dspp
promoter
by
Trps
1
.
During
tooth
development
Trps
1
is
highly
expressed
in
preodontoblasts
,
but
in
mature
odontoblasts
secreting
matrix
its
expression
significantly
decreases
,
which
suggests
a
Trps
1
role
in
odontoblast
development
.
In
these
studies
we
identified
Trps
1
as
a
potent
inhibitor
of
Dspp
expression
and
the
subsequent
mineralization
of
dentin
.
Thus
,
we
provide
novel
insights
into
mechanisms
of
transcriptional
dysregulation
that
leads
to
DGI
.
Diseases
Validation
Diseases presenting
"dentinogenesis imperfecta"
symptom
dentin dysplasia
dentinogenesis imperfecta
oligodontia
papillon-lefèvre syndrome
This symptom has already been validated
