Cell type-specific expression, regulation and compensation of CDKL5 activity in mouse brain.

ABSTRACT: CDKL5 is a brain-enriched serine/threonine kinase, associated with a profound developmental and epileptic encephalopathy called CDKL5 deficiency disorder (CDD). To design targeted therapies for CDD, it is essential to determine where CDKL5 is expressed and is active in the brain and test if compensatory mechanisms exist at cellular level. We generated conditional Cdkl5 knockout mice in excitatory neurons, inhibitory neurons and astrocytes. To assess CDKL5 activity, we utilized a phosphospecific antibody for phosphorylated EB2, a well-known substrate of CDKL5. We found that CDKL5 and EB2 pS222 were prominent in excitatory and inhibitory neurons but were not detected in astrocytes. We observed that approximately 15-20% of EB2 pS222 remained in Cdkl5 knockout brains and primary neurons. Surpr

SUBMITTER: Silvestre M 

PROVIDER: S-EPMC11371643 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature