Autistic-relevant behavioral phenotypes of a mouse model of cyclin-dependent kinase-like 5 deficiency disorder.
Cdkl5-lacking mice show lifelong social and communication deficits, offering a stable petri dish for autism intervention trials.
01Research in Context
What this study did
Mottolese et al. (2024) watched Cdkl5-KO mice from baby to adult. They tracked calls, play, and repetitive moves.
The team wanted a full map of autism-like traits in this rare-disease model.
What they found
The mice made fewer baby cries, played less with partners, and showed more anxious circling. Both sexes kept these problems for life.
Early deficits stayed, they did not fade.
How this fits with other research
Gaudissard et al. (2017) saw the opposite fade in Fmr1-KO2 mice: social problems vanished after youth. The new Cdkl5 data show some autism genes keep hurting, others quiet down.
Quesnel et al. (2026) found male-only brain shrinkage in ATRX mice, while Nicola saw equal social hits in both sexes. Method gap: ATRX scanned brains, Cdkl5 scored deeds.
Cheng et al. (2017) also caught early, life-long wiring faults in BTBR mice. Together the papers argue: test early, track long, pick the right model for your question.
Why it matters
If you run drug or skill studies, pick models with stable phenotypes. Cdkl5 mice give you lasting social and communication targets, unlike Fmr1 lines where social ills melt with age. Use ultrasonic call counts or social-sniff time as cheap, quick probes in pilot work.
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02At a glance
03Original abstract
Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene and characterized by early-onset epilepsy, intellectual disability, and autistic features. To date, the etiological mechanisms underlying CDD are largely unknown and no effective therapies are available. The Cdkl5 knock-out (KO) mouse has been broadly employed in preclinical studies on CDD; Cdkl5-KO mice display neurobehavioral abnormalities recapitulating most CDD symptoms, including alterations in motor, sensory, cognitive, and social abilities. However, most available preclinical studies have been carried out on adult Cdkl5-KO mice, so little is known about the phenotypic characteristics of this model earlier during development. Furthermore, major autistic-relevant phenotypes, for example, social and communication deficits, have been poorly investigated and mostly in male mutants. Here, we assessed the autistic-relevant behavioral phenotypes of Cdkl5-KO mice during the first three post-natal weeks and in adulthood. Males and females were tested, the latter including both heterozygous and homozygous mutants. Cdkl5 mutant pups showed qualitative and quantitative alterations in ultrasonic communication, detected first at 2 weeks of age and confirmed later in adulthood. Increased levels of anxiety-like behaviors were observed in mutants at 3 weeks and in adulthood, when stereotypies, reduced social interaction and memory deficits were also observed. These behavioral effects of the mutation were evident in both sexes, being more marked and varied in homozygous than heterozygous females. These findings provide novel evidence for the autistic-relevant behavioral profile of the Cdkl5 mouse model, thus supporting its use in future preclinical studies investigating CDD pathology and autism spectrum disorders.
Autism research : official journal of the International Society for Autism Research, 2024 · doi:10.1002/aur.3226