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| Title | Deficiency of cyclin-dependent kinase-like 5 causes spontaneous epileptic seizures in neonatal mice |
| Creator | 廖文霖 Liao, Wenlin Kun-Ze Lee Jinchung Chen San-Hua Su Yuju Luo |
| Contributor | 神科所 |
| Date | 2020-03 |
| Date Issued | 13-Nov-2020 15:40:55 (UTC+8) |
| Summary | Cyclin-dependent kinase-like 5 (CDKL5), an X-linked gene encoding a serine-threonine kinase, is enriched in the mammalian forebrain and critical for neuronal maturation and synaptic function. Mutations in this gene cause CDKL5 deficiency disorder (CDD), which is characterized by early-onset epileptic seizures, motor dysfunction and intellectual disability. Although several mouse models for CDD have been developed, overt spontaneous seizures have not been reported in adult mice with CDKL5 deficiency. Here, we present the first systematic study of spontaneous seizures in a mouse model of CDD. Through wireless electroencephalography (EEG) recording in a longitudinal manner, we observed epileptiform discharges in pups lacking CDKL5. The total number of spike events, the total burst number and burst duration were significantly increased in Cdkl5 null pups at the age of postnatal day 12 (P12). With age, these seizure-like discharges gradually diminished in mutant pups, while the discharges increased progressively in wild-type mice. Through simultaneous videotaping, Cdkl5 null pups exhibited seizure-like behaviors during prolonged bursts of discharges at P12, and showed increased ictal grasping and grip strength in adults. Notably, loss of CDKL5 remarkably down-regulated the phosphorylation of K+-Cl- co-transporter 2 (KCC2) in the cortex and hippocampus at P12. Our findings reveal a previously unidentified age-dependent phenotype of early-onset seizures in CDKL5-deficient neonatal mice, enhancing the translational value of CDD mouse model and providing a potential molecular target for early diagnosis and therapeutic development for CDD. |
| Relation | bioRxiv, pp.1-37 |
| Type | article |
| DOI | https://doi.org/10.1101/2020.03.09.983981 |
| dc.contributor | 神科所 | - |
| dc.creator (作者) | 廖文霖 | - |
| dc.creator (作者) | Liao, Wenlin | - |
| dc.creator (作者) | Kun-Ze Lee | - |
| dc.creator (作者) | Jinchung Chen | - |
| dc.creator (作者) | San-Hua Su | - |
| dc.creator (作者) | Yuju Luo | - |
| dc.date (日期) | 2020-03 | - |
| dc.date.accessioned | 13-Nov-2020 15:40:55 (UTC+8) | - |
| dc.date.available | 13-Nov-2020 15:40:55 (UTC+8) | - |
| dc.date.issued (上傳時間) | 13-Nov-2020 15:40:55 (UTC+8) | - |
| dc.identifier.uri (URI) | http://nccur.lib.nccu.edu.tw/handle/140.119/132554 | - |
| dc.description.abstract (摘要) | Cyclin-dependent kinase-like 5 (CDKL5), an X-linked gene encoding a serine-threonine kinase, is enriched in the mammalian forebrain and critical for neuronal maturation and synaptic function. Mutations in this gene cause CDKL5 deficiency disorder (CDD), which is characterized by early-onset epileptic seizures, motor dysfunction and intellectual disability. Although several mouse models for CDD have been developed, overt spontaneous seizures have not been reported in adult mice with CDKL5 deficiency. Here, we present the first systematic study of spontaneous seizures in a mouse model of CDD. Through wireless electroencephalography (EEG) recording in a longitudinal manner, we observed epileptiform discharges in pups lacking CDKL5. The total number of spike events, the total burst number and burst duration were significantly increased in Cdkl5 null pups at the age of postnatal day 12 (P12). With age, these seizure-like discharges gradually diminished in mutant pups, while the discharges increased progressively in wild-type mice. Through simultaneous videotaping, Cdkl5 null pups exhibited seizure-like behaviors during prolonged bursts of discharges at P12, and showed increased ictal grasping and grip strength in adults. Notably, loss of CDKL5 remarkably down-regulated the phosphorylation of K+-Cl- co-transporter 2 (KCC2) in the cortex and hippocampus at P12. Our findings reveal a previously unidentified age-dependent phenotype of early-onset seizures in CDKL5-deficient neonatal mice, enhancing the translational value of CDD mouse model and providing a potential molecular target for early diagnosis and therapeutic development for CDD. | - |
| dc.format.extent | 5725050 bytes | - |
| dc.format.mimetype | application/pdf | - |
| dc.relation (關聯) | bioRxiv, pp.1-37 | - |
| dc.title (題名) | Deficiency of cyclin-dependent kinase-like 5 causes spontaneous epileptic seizures in neonatal mice | - |
| dc.type (資料類型) | article | - |
| dc.identifier.doi (DOI) | 10.1101/2020.03.09.983981 | - |
| dc.doi.uri (DOI) | https://doi.org/10.1101/2020.03.09.983981 | - |