CDKL5 Deficiency Disorder (CDD) is an X-linked developmental encephalopathy. Characteristics of the disorder include: intractable seizures, severe neurodevelopmental delay, intellectual disability, autistic features, and motor impairment. The overall incidence of CDD is 1 in 42,000 births. Because this disorder is X-linked, CDD predominantly affects females (heterozygous) and affects few males (hemizygous).

CDKL5 is a serine-threonine kinase located in the Xp22 region. CDKL5 shows homology with CDKs and MAPKs. CDKL5 consists of 23 coding exons and is highly expressed in the brain.

CDD is caused by mutations in the CDKL5 gene. Most missense mutations occur in the catalytic domain, and nonsense mutations that occur cause truncation and mRNA decay. Mutations in the CDKL5 gene, whether it be missense or nonsense, disrupt CDKL5 function, leading to CDD at varying severities depending on the severity of the mutation. Little is known about the function and pathophysiology of CDKL5 in humans and there is no established treatment for CDD. To study this, the Zhou lab and others have generated mouse models of CDKL5, recapitulating many key features of CDD, studying them in many different lenses.

Currently, there are several mouse models that recapitulate CDD. In this presentation, I will be going over the observations and characteristics of each model.