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2016 ; 91
(ä): 284-91
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MECP2 impairs neuronal structure by regulating KIBRA
#MMPMID27015692
Williams AA
; White R
; Siniard A
; Corneveaux J
; Huentelman M
; Duch C
Neurobiol Dis
2016[Jul]; 91
(ä): 284-91
PMID27015692
show ga
Using a Drosophila model of MECP2 gain-of-function, we identified memory
associated KIBRA as a target of MECP2 in regulating dendritic growth. We found
that expression of human MECP2 increased kibra expression in Drosophila, and
targeted RNAi knockdown of kibra in identified neurons fully rescued dendritic
defects as induced by MECP2 gain-of-function. Validation in mouse confirmed that
Kibra is similarly regulated by Mecp2 in a mammalian system. We found that Mecp2
gain-of-function in cultured mouse cortical neurons caused dendritic impairments
and increased Kibra levels. Accordingly, Mecp2 loss-of-function in vivo led to
decreased Kibra levels in hippocampus, cortex, and cerebellum. Together, our
results functionally link two neuronal genes of high interest in human health and
disease and highlight the translational utility of the Drosophila model for
understanding MECP2 function.