Human Molecular Genetics,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 16, 2025
Abstract
Laminin
B1
(LAMB1)
is
one
of
the
extracellular
matrix
(ECM)
proteins
that
make
up
basement
membrane.
Early
frameshift,
late
and
missense
variants
in
LAMB1
have
been
reported
to
cause
rare
monogenic
neurological
disorders
are
collectively
known
as
LAMB1-related
leukoencephalopathy.
Although
there
some
genotype–phenotype
correlation,
functional
consequences
pathogenic
largely
unknown.
In
this
study,
we
aimed
elucidate
function
fly
ortholog
gene
(LanB1)
nervous
system
further
study
using
Drosophila
melanogaster.
We
found
LanB1
expressed
on
surface
adult
brains
a
subset
glia
cells.
protein
localizes
blood–brain
barrier
(BBB)
knockdown
BBB
resulted
short
life
span
locomotor
defects.
human
was
not
able
flies,
vivo
overexpression
rescue
experiments
analogous
suggested
frameshift
behave
strong
loss-of-function
(LoF)
alleles
whereas
variant
functions
milder
LoF
allele.
vitro
assay
HEK293T
cells
revealed
late-truncated
uniquely
detected
monomer
culture
medium,
which
might
be
basis
dominant
inheritance
these
through
gain-of-function
mechanism.
Our
data
contributes
understanding
ECM
component
lays
foundation
unravel
molecular
different
LAMB1.
Abstract
FlyBase
(flybase.org)
is
a
model
organism
database
and
knowledge
base
about
Drosophila
melanogaster,
commonly
known
as
the
fruit
fly.
Researchers
from
around
world
rely
on
genetic,
genomic,
functional
information
available
in
FlyBase,
well
its
tools
to
view
interrogate
these
data.
In
this
article,
we
describe
latest
developments
updates
FlyBase.
These
include
introduction
of
single-cell
RNA
sequencing
data,
improved
content
display
information,
updated
orthology
pipelines,
new
chemical
reports,
enhancements
our
outreach
resources.
Frontiers in Neuroscience,
Год журнала:
2023,
Номер
17
Опубликована: Фев. 16, 2023
Neurodegenerative
Diseases
(NDDs)
are
a
group
of
disorders
that
cause
progressive
deficits
neuronal
function.
Recent
evidence
argues
sphingolipid
metabolism
is
affected
in
surprisingly
broad
set
NDDs.
These
include
some
lysosomal
storage
diseases
(LSDs),
hereditary
sensory
and
autonomous
neuropathy
(HSAN),
spastic
paraplegia
(HSP),
infantile
neuroaxonal
dystrophy
(INAD),
Friedreich’s
ataxia
(FRDA),
as
well
forms
amyotrophic
lateral
sclerosis
(ALS)
Parkinson’s
disease
(PD).
Many
these
have
been
modeled
Drosophila
melanogaster
associated
with
elevated
levels
ceramides.
Similar
changes
also
reported
vertebrate
cells
mouse
models.
Here,
we
summarize
studies
using
fly
models
and/or
patient
samples
which
demonstrate
the
nature
defects
metabolism,
organelles
implicated,
cell
types
initially
affected,
potential
therapeutics
for
diseases.
Frontiers in Molecular Neuroscience,
Год журнала:
2023,
Номер
16
Опубликована: Фев. 16, 2023
Epilepsy
is
one
of
the
most
prevalent
neurological
disorders,
affecting
more
than
45
million
people
worldwide.
Recent
advances
in
genetic
techniques,
such
as
next-generation
sequencing,
have
driven
discovery
and
increased
our
understanding
molecular
cellular
mechanisms
behind
many
epilepsy
syndromes.
These
insights
prompt
development
personalized
therapies
tailored
to
characteristics
an
individual
patient.
However,
surging
number
novel
variants
renders
interpretation
pathogenetic
consequences
potential
therapeutic
implications
ever
challenging.
Model
organisms
can
help
explore
these
aspects
vivo
.
In
last
decades,
rodent
models
significantly
contributed
epilepsies
but
their
establishment
laborious,
expensive,
time-consuming.
Additional
model
investigate
disease
on
a
large
scale
would
be
desirable.
The
fruit
fly
Drosophila
melanogaster
has
been
used
organism
research
since
“bang-sensitive”
mutants
half
century
ago.
flies
respond
mechanical
stimulation,
brief
vortex,
with
stereotypic
seizures
paralysis.
Furthermore,
identification
seizure-suppressor
mutations
allows
pinpoint
targets.
Gene
editing
CRISPR/Cas9,
are
convenient
way
generate
carrying
disease-associated
variants.
screened
for
phenotypic
behavioral
abnormalities,
shifting
seizure
thresholds,
response
anti-seizure
medications
other
substances.
Moreover,
modification
neuronal
activity
induction
achieved
using
optogenetic
tools.
combination
calcium
fluorescent
imaging,
functional
alterations
caused
by
genes
traced.
Here,
we
review
versatile
study
epilepsies,
especially
81%
human
orthologous
gene
discuss
newly
established
analysis
techniques
that
might
further
unravel
pathophysiological
epilepsies.
