Cyclin-dependent kinase-like 5 (Cdkl5) is an X-linked gene encoding a serine/threonine kinase that is highly expressed in the brain. Genetic mutations that disrupt CDKL5 function have been found in humans with neurodevelopmental disorders including atypical Rett syndrome (RTT), autism spectrum disorders (ASDs), and early infantile epileptic encephalopathy 2 (EIEE2). These individuals, classified under CDKL5 Disorder for the common genetic defect, are characterized by early-onset seizures, intellectual disability, and autistic features.
Cdkl5 knockout mice, lacking exon 6 of Cdkl5 (corresponding to exon 7 of human CDKL5), were developed to mimic a splice mutation found in humans that results in the skipping of exon 7, generating a premature stop codon and really truncation CDKL5 in its N-terminal kinase domain. Male carriers show autistic-like behavioral abnormalities, hyperactivity, motor impairments, decreased anxiety, deficits in social interaction, and impaired learning and memory with absence of spontaneous seizures. They also exhibit deficits in neural circuit communication. Cdkl5 knockout males have alterations in phosphorylation profiles in forebrain regions including the striatum, somatosensory cortex, and hippocampus where CDKL5 is expressed. Multiple signal transduction pathways, including AKT-mTOR cascade, are disrupted in Cdkl5 knockout mice. Mice that are homozygous for this allele are viable and fertile.
Of note, the floxed version of this allele is available as Stock No. 030523.
