A novel mouse model of creatine transporter deficiency [v1; ref status: indexed, http://f1000r.es/4f8]
Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and behavioral disturbances, language and speech impairment ( OMI...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2014-09-01
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| Online Access: | http://f1000research.com/articles/3-228/v1 |
| _version_ | 1828863012779327488 |
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| author | Laura Baroncelli Maria Grazia Alessandrì Jonida Tola Elena Putignano Martina Migliore Elena Amendola Cornelius Gross Vincenzo Leuzzi Giovanni Cioni Tommaso Pizzorusso |
| author_facet | Laura Baroncelli Maria Grazia Alessandrì Jonida Tola Elena Putignano Martina Migliore Elena Amendola Cornelius Gross Vincenzo Leuzzi Giovanni Cioni Tommaso Pizzorusso |
| author_sort | Laura Baroncelli |
| collection | DOAJ |
| description | Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and behavioral disturbances, language and speech impairment ( OMIM #300352). CCDS1 is still an untreatable pathology that can be very invalidating for patients and caregivers. Only two murine models of CCDS1, one of which is an ubiquitous knockout mouse, are currently available to study the possible mechanisms underlying the pathologic phenotype of CCDS1 and to develop therapeutic strategies. Given the importance of validating phenotypes and efficacy of promising treatments in more than one mouse model we have generated a new murine model of CCDS1 obtained by ubiquitous deletion of 5-7 exons in the Slc6a8 gene. We showed a remarkable Cr depletion in the murine brain tissues and cognitive defects, thus resembling the key features of human CCDS1. These results confirm that CCDS1 can be well modeled in mice. This CrT−/y murine model will provide a new tool for increasing the relevance of preclinical studies to the human disease. |
| first_indexed | 2024-12-13T03:35:23Z |
| format | Article |
| id | doaj.art-3e98df52c28f41d8b4ab16f80c3b969b |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-13T03:35:23Z |
| publishDate | 2014-09-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-3e98df52c28f41d8b4ab16f80c3b969b2022-12-22T00:01:03ZengF1000 Research LtdF1000Research2046-14022014-09-01310.12688/f1000research.5369.15732A novel mouse model of creatine transporter deficiency [v1; ref status: indexed, http://f1000r.es/4f8]Laura Baroncelli0Maria Grazia Alessandrì1Jonida Tola2Elena Putignano3Martina Migliore4Elena Amendola5Cornelius Gross6Vincenzo Leuzzi7Giovanni Cioni8Tommaso Pizzorusso9Institute of Neuroscience, National Research Council (CNR), Pisa, I-56124, ItalyDepartment of Developmental Neuroscience, IRCCS Stella Maris Scientific Institute, Calambrone (Pisa), I-56128, ItalyInstitute of Neuroscience, National Research Council (CNR), Pisa, I-56124, ItalyInstitute of Neuroscience, National Research Council (CNR), Pisa, I-56124, ItalyInstitute of Neuroscience, National Research Council (CNR), Pisa, I-56124, ItalyMouse Biology Unit, European Molecular Biology Laboratory (EMBL), Monterotondo (Roma), I-00015, ItalyMouse Biology Unit, European Molecular Biology Laboratory (EMBL), Monterotondo (Roma), I-00015, ItalyDepartment of Paediatrics, Child Neurology and Psychiatry, Sapienza University of Rome, Rome, I-00185, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, I-56126, ItalyDepartment of Neuroscience, Psychology, Drug Research and Child Health NEUROFARBA, University of Florence, Florence, I-50135, ItalyMutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and behavioral disturbances, language and speech impairment ( OMIM #300352). CCDS1 is still an untreatable pathology that can be very invalidating for patients and caregivers. Only two murine models of CCDS1, one of which is an ubiquitous knockout mouse, are currently available to study the possible mechanisms underlying the pathologic phenotype of CCDS1 and to develop therapeutic strategies. Given the importance of validating phenotypes and efficacy of promising treatments in more than one mouse model we have generated a new murine model of CCDS1 obtained by ubiquitous deletion of 5-7 exons in the Slc6a8 gene. We showed a remarkable Cr depletion in the murine brain tissues and cognitive defects, thus resembling the key features of human CCDS1. These results confirm that CCDS1 can be well modeled in mice. This CrT−/y murine model will provide a new tool for increasing the relevance of preclinical studies to the human disease.http://f1000research.com/articles/3-228/v1Behavioral NeuroscienceNeurogenetics |
| spellingShingle | Laura Baroncelli Maria Grazia Alessandrì Jonida Tola Elena Putignano Martina Migliore Elena Amendola Cornelius Gross Vincenzo Leuzzi Giovanni Cioni Tommaso Pizzorusso A novel mouse model of creatine transporter deficiency [v1; ref status: indexed, http://f1000r.es/4f8] F1000Research Behavioral Neuroscience Neurogenetics |
| title | A novel mouse model of creatine transporter deficiency [v1; ref status: indexed, http://f1000r.es/4f8] |
| title_full | A novel mouse model of creatine transporter deficiency [v1; ref status: indexed, http://f1000r.es/4f8] |
| title_fullStr | A novel mouse model of creatine transporter deficiency [v1; ref status: indexed, http://f1000r.es/4f8] |
| title_full_unstemmed | A novel mouse model of creatine transporter deficiency [v1; ref status: indexed, http://f1000r.es/4f8] |
| title_short | A novel mouse model of creatine transporter deficiency [v1; ref status: indexed, http://f1000r.es/4f8] |
| title_sort | novel mouse model of creatine transporter deficiency v1 ref status indexed http f1000r es 4f8 |
| topic | Behavioral Neuroscience Neurogenetics |
| url | http://f1000research.com/articles/3-228/v1 |
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