Rare Diseases Symptoms Automatic Extraction
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Deletion of PREPl causes growth impairment and hypotonia in mice.
[cystinuria]
Genetic
studies
of
rare
diseases
can
identify
genes
of
unknown
function
that
strongly
impact
human
physiology
.
Prolyl
endopeptidase-like
(
PREPL
)
is
an
uncharacterized
member
of
the
prolyl
peptidase
family
that
was
discovered
because
of
its
deletion
in
humans
with
hypotonia
-
cystinuria
syndrome
(
HCS
)
.
HCS
is
characterized
by
a
number
of
physiological
changes
including
diminished
growth
and
neonatal
hypotonia
or
low
muscle
tone
.
HCS
patients
have
deletions
in
other
genes
as
well
,
making
it
difficult
to
tease
apart
the
specific
role
of
PREPL
.
Here
,
we
develop
a
PREPL
null
(
PREPL
(
-
/
-
)
)
mouse
model
to
address
the
physiological
role
of
this
enzyme
.
Deletion
of
exon
11
from
the
Prepl
gene
,
which
encodes
key
catalytic
amino
acids
,
leads
to
a
loss
of
PREPL
protein
as
well
as
lower
Prepl
mRNA
levels
.
PREPL
(
-
/
-
)
mice
have
a
pronounced
growth
phenotype
,
being
significantly
shorter
and
lighter
than
their
wild
type
(
PREPL
(
+
/
+
)
)
counterparts
.
A
righting
assay
revealed
that
PREPL
(
-
/
-
)
pups
took
significantly
longer
than
PREPL
(
+
/
+
)
pups
to
right
themselves
when
placed
on
their
backs
.
This
deficit
indicates
that
PREPL
(
-
/
-
)
mice
suffer
from
neonatal
hypotonia
.
According
to
these
results
,
PREPL
regulates
growth
and
neonatal
hypotonia
in
mice
,
which
supports
the
idea
that
PREPL
causes
diminished
growth
and
neonatal
hypotonia
in
humans
with
HCS
.
These
animals
provide
a
valuable
asset
in
deciphering
the
underlying
biochemical
,
cellular
and
physiological
pathways
that
link
PREPL
to
HCS
,
and
this
may
eventually
lead
to
new
insights
in
the
treatment
of
this
disease
.