Mice lacking cyclin-dependent kinase-like 5 manifest autistic and ADHD-like behaviors
| Autor: | Yi-Ping Hsueh, Wenlin Liao, Cian-Ling Jhang, Tzyy-Nan Huang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Autism Spectrum Disorder Dopamine CDKL5 Hyperkinesis Protein Serine-Threonine Kinases Biology Impulsivity behavioral disciplines and activities Mice 03 medical and health sciences 0302 clinical medicine Neurodevelopmental disorder Genes X-Linked mental disorders Genetics medicine Animals Attention deficit hyperactivity disorder Autistic Disorder Molecular Biology Genetics (clinical) Mice Knockout Brain General Medicine medicine.disease Comorbidity Associative learning Mice Inbred C57BL Disease Models Animal 030104 developmental biology Attention Deficit Disorder with Hyperactivity Autism medicine.symptom Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Human Molecular Genetics. 26:3922-3934 |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | Neurodevelopmental disorders frequently share common clinical features and appear high rate of comorbidity, such as those present in patients with attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). While characterizing behavioral phenotypes in the mouse model of cyclin-dependent kinase-like 5 (CDKL5) disorder, a neurodevelopmental disorder caused by mutations in the X-linked gene encoding CDKL5, we found that these mice manifested behavioral phenotypes mimicking multiple key features of ASD, such as impaired social interaction and communication, as well as increased stereotypic digging behaviors. These mice also displayed hyper-locomotion, increased aggressiveness and impulsivity, plus deficits in motor and associative learning, resembling primary symptoms of ADHD. Through brain region-specific biochemical analysis, we uncovered that loss of CDKL5 disrupts dopamine synthesis and the expression of social communication-related key genes, such as forkhead-box P2 and mu-opioid receptor, in the corticostriatal circuit. Together, our findings support that CDKL5 plays a role in the comorbid features of autism and ADHD, and mice lacking CDKL5 may serve as an animal model to study the molecular and circuit mechanisms underlying autism-ADHD comorbidity. |
| Databáze: | OpenAIRE |
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