Mapping pathological phenotypes in a mouse model of CDKL5 disorder.
Mutations in cyclin-dependent kinase-like 5 (CDKL5) cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. B...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2014
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/d45b19ecb62749ff9f027ee1b74272dc |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:d45b19ecb62749ff9f027ee1b74272dc |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:d45b19ecb62749ff9f027ee1b74272dc2021-11-18T08:18:52ZMapping pathological phenotypes in a mouse model of CDKL5 disorder.1932-620310.1371/journal.pone.0091613https://doaj.org/article/d45b19ecb62749ff9f027ee1b74272dc2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24838000/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Mutations in cyclin-dependent kinase-like 5 (CDKL5) cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG) responses to convulsant treatment, decreased visual evoked responses (VEPs), and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder.Elena AmendolaYang ZhanCamilla MattucciEnrico CastroflorioEleonora CalcagnoClaudia FuchsGiuseppina LonettiDavide SilingardiAlexei L VyssotskiDominika FarleyElisabetta CianiTommaso PizzorussoMaurizio GiustettoCornelius T GrossPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e91613 (2014) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Elena Amendola Yang Zhan Camilla Mattucci Enrico Castroflorio Eleonora Calcagno Claudia Fuchs Giuseppina Lonetti Davide Silingardi Alexei L Vyssotski Dominika Farley Elisabetta Ciani Tommaso Pizzorusso Maurizio Giustetto Cornelius T Gross Mapping pathological phenotypes in a mouse model of CDKL5 disorder. |
| description |
Mutations in cyclin-dependent kinase-like 5 (CDKL5) cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG) responses to convulsant treatment, decreased visual evoked responses (VEPs), and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder. |
| format |
article |
| author |
Elena Amendola Yang Zhan Camilla Mattucci Enrico Castroflorio Eleonora Calcagno Claudia Fuchs Giuseppina Lonetti Davide Silingardi Alexei L Vyssotski Dominika Farley Elisabetta Ciani Tommaso Pizzorusso Maurizio Giustetto Cornelius T Gross |
| author_facet |
Elena Amendola Yang Zhan Camilla Mattucci Enrico Castroflorio Eleonora Calcagno Claudia Fuchs Giuseppina Lonetti Davide Silingardi Alexei L Vyssotski Dominika Farley Elisabetta Ciani Tommaso Pizzorusso Maurizio Giustetto Cornelius T Gross |
| author_sort |
Elena Amendola |
| title |
Mapping pathological phenotypes in a mouse model of CDKL5 disorder. |
| title_short |
Mapping pathological phenotypes in a mouse model of CDKL5 disorder. |
| title_full |
Mapping pathological phenotypes in a mouse model of CDKL5 disorder. |
| title_fullStr |
Mapping pathological phenotypes in a mouse model of CDKL5 disorder. |
| title_full_unstemmed |
Mapping pathological phenotypes in a mouse model of CDKL5 disorder. |
| title_sort |
mapping pathological phenotypes in a mouse model of cdkl5 disorder. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/d45b19ecb62749ff9f027ee1b74272dc |
| work_keys_str_mv |
AT elenaamendola mappingpathologicalphenotypesinamousemodelofcdkl5disorder AT yangzhan mappingpathologicalphenotypesinamousemodelofcdkl5disorder AT camillamattucci mappingpathologicalphenotypesinamousemodelofcdkl5disorder AT enricocastroflorio mappingpathologicalphenotypesinamousemodelofcdkl5disorder AT eleonoracalcagno mappingpathologicalphenotypesinamousemodelofcdkl5disorder AT claudiafuchs mappingpathologicalphenotypesinamousemodelofcdkl5disorder AT giuseppinalonetti mappingpathologicalphenotypesinamousemodelofcdkl5disorder AT davidesilingardi mappingpathologicalphenotypesinamousemodelofcdkl5disorder AT alexeilvyssotski mappingpathologicalphenotypesinamousemodelofcdkl5disorder AT dominikafarley mappingpathologicalphenotypesinamousemodelofcdkl5disorder AT elisabettaciani mappingpathologicalphenotypesinamousemodelofcdkl5disorder AT tommasopizzorusso mappingpathologicalphenotypesinamousemodelofcdkl5disorder AT mauriziogiustetto mappingpathologicalphenotypesinamousemodelofcdkl5disorder AT corneliustgross mappingpathologicalphenotypesinamousemodelofcdkl5disorder |
| _version_ |
1718421953295941632 |