Phenotypic Characterization of Cdkl5-knockdown Neurons Establishes Elongated Cilia As a Functional Assay for CDKL5 Deficiency Disorder

Overview

Journal Neurosci Res

Publisher Elsevier

Specialty Neurology

Date 2021 Oct 8

PMID 34624412

Citations 12

Authors

Alessia Di Nardo

Alina Ruhmkorf

Patricia Award

Ashton Brennecke

Michela Fagiolini

Mustafa Sahin

Affiliations

Soon will be listed here.

Abstract

CDKL5 Deficiency Disorder (CDD) is a severe encephalopathy characterized by intractable epilepsy, infantile spasms, and cognitive disabilities. The detrimental CNS manifestations and lack of therapeutic interventions represent unmet needs, necessitating identification of CDD-dependent phenotypes for in vitro disease modeling and therapeutic testing. Here, we optimized a high-content assay to quantify cilia in CDKL5-deficient neurons. Our work shows that Cdkl5-knockdown neurons have elongated cilia and uncovers cilium lengthening in hippocampi of Cdkl5 knockout mice. Collectively, our findings identify cilia length alterations under CDKL5 activity loss in vitro and in vivo and reveal elongated cilia as a robust functional phenotype for CDD.

Citing Articles

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