Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Tbx5-mediated expression of Ca(2+)/calmodulin-dependent protein kinase II is necessary for zebrafish cardiac and pectoral fin morphogenesis.
[holt-oram syndrome]
Mutations
in
the
T
-
box
transcription
factor
,
TBX
5
,
result
in
Holt-
Oram
syndrome
(
HOS
)
,
a
human
condition
in
which
cardiac
development
is
defective
and
forelimbs
are
stunted
.
Similarly
,
zebrafish
tbx
5
morphants
and
mutants
(
heartstrings
;
hst
)
lack
pectoral
fins
and
exhibit
a
persistently
elongated
heart
that
does
not
undergo
chamber
looping
.
Tbx
5
is
expressed
in
the
developing
atrium
,
ventricle
and
in
pectoral
fin
fields
,
but
its
genetic
targets
are
still
being
uncovered
.
In
this
study
,
evidence
is
provided
that
Tbx
5
induces
the
expression
of
a
specific
member
of
the
CaMK-
II
(
the
type
II
multifunctional
Ca
(
2
+
)
/
calmodulin-dependent
protein
kinase
)
family
;
this
CaMK-
II
is
necessary
for
proper
heart
and
fin
development
.
Morphants
of
beta
2
CaMK-
II
(
camk
2
b
2
)
,
but
not
the
beta
1
CaMK-
II
(
camk
2
b
1
)
paralog
,
exhibit
bradycardia
,
elongated
hearts
and
diminished
pectoral
fin
development
.
Normal
cardiac
phenotypes
can
be
restored
by
ectopic
cytosolic
CaMK-
II
expression
in
tbx
5
morphants
.
Like
tbx
5
,
camk
2
b
2
is
expressed
in
the
pectoral
fin
and
looping
heart
,
but
this
expression
is
diminished
in
both
tbx
5
morphant
and
hst
embryos
.
Conversely
,
the
introduction
of
excess
Tbx
5
into
zebrafish
embryos
and
mouse
fibroblasts
doubles
CaMK-
II
expression
.
We
conclude
that
beta
CaMK-
II
expression
and
activity
are
necessary
for
proper
cardiac
and
limb
morphogenesis
.
These
findings
not
only
identify
a
morphogenic
target
for
Ca
(
2
+
)
during
heart
development
,
but
support
implied
roles
for
CaMK-
II
in
adult
heart
remodeling
.
Diseases
Validation
Diseases presenting
"specific member of the camk-ii"
symptom
holt-oram syndrome
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom