¸ñÀû: Olfactory dysfunction, such as anosmia or hyposmia, is a recognized
symptom of ciliopathies, which are multiple genetic disorders arising
from abnormalities in cilia assembly, maintenance, and/or function in
both humans and animal models. The positioning of the centrioles (basal
bodies) to the OSN knob during OSN development is crucial for
ciliogenesis, where cilia form on the knob surface and extend in the
direction of the airway. However, the mechanism by which the centriole-
derived basal body positions itself on the cell surface to serve as the
template for cilium formation remains unclear. ¹æ¹ý:1. Since homozygous knockout of Kif3a in mice is embryonic lethal, we
generated mice with OMP-specific inactivation of Kif3a induced by Cre-
recombinase under the olfactory marker protein (OMP) promoter (OMP-
cre;Kif3aflox/flox). 2. We performed primary phenotyping to investigate
whether OMP- cre;Kif3aflox/flox, generated through odorant behavior
tests, perceive odors. Additionally, we conducted secondary phenotyping
using electro- olfactogram to examine the functional abnormalities of
OMP- cre;Kif3aflox/flox OSNs. 3. We investigated histopathological
abnormalities such as knob formation, ciliogenesis, and centriole
positioning in OMP- cre;Kif3aflox/flox mouse OSNs using transmission
electron microscopy (TEM), scanning electron microscopy (SEM), and
immunohistochemistry. 4. We induced ciliogenesis in cultured cells and
subsequently treated them with a microtubule depolymerizing reagent to
investigate whether centriole migration is closely related to
microtubules associated with Kif3a in our in vitro study. °á°ú:We generated mice with OMP-specific inactivation of Kif3a induced by
Cre-recombinase under the olfactory marker protein (OMP) promoter. This
model exhibited impaired smell perception, as evidenced by odorant
behavior tests and electro-olfactogram recordings. Histopathological
analysis revealed severely abnormal knob formation and significant
defects in cilia formation in the OSNs. Notably, numerous centrioles
were found to be ectopically localized on the OSN dendrite. Furthermore,
an in vitro study using nocodazole treatment demonstrated that centriole
positioning during ciliogenesis depends closely on microtubules
associated with Kif3a function. °á·Ð:These findings suggest that the lack of Kif3a leads to noticeable
disruptions in centriole positioning, ultimately impacting the intricate
process of olfactory sensory neuron development. |