Micro-CT Imaging Reveals Mekk3 Heterozygosity Prevents Cerebral Cavernous Malformations in Ccm2-Deficient Mice.
- Publisher:
- PUBLIC LIBRARY SCIENCE
- Publication Type:
- Journal Article
- Citation:
- PLoS One, 2016, 11, (8), pp. e0160833
- Issue Date:
- 2016
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Choi, JP | |
dc.contributor.author | Foley, M | |
dc.contributor.author | Zhou, Z | |
dc.contributor.author | Wong, W-Y | |
dc.contributor.author | Gokoolparsadh, N | |
dc.contributor.author | Arthur, JSC | |
dc.contributor.author | Li, DY | |
dc.contributor.author | Zheng, X | |
dc.date.accessioned | 2022-08-13T06:41:49Z | |
dc.date.available | 2016-07-26 | |
dc.date.available | 2022-08-13T06:41:49Z | |
dc.date.issued | 2016 | |
dc.identifier.citation | PLoS One, 2016, 11, (8), pp. e0160833 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/10453/160071 | |
dc.description.abstract | Mutations in CCM1 (aka KRIT1), CCM2, or CCM3 (aka PDCD10) gene cause cerebral cavernous malformation in humans. Mouse models of CCM disease have been established by deleting Ccm genes in postnatal animals. These mouse models provide invaluable tools to investigate molecular mechanism and therapeutic approaches for CCM disease. However, the full value of these animal models is limited by the lack of an accurate and quantitative method to assess lesion burden and progression. In the present study we have established a refined and detailed contrast enhanced X-ray micro-CT method to measure CCM lesion burden in mouse brains. As this study utilized a voxel dimension of 9.5μm (leading to a minimum feature size of approximately 25μm), it is therefore sufficient to measure CCM lesion volume and number globally and accurately, and provide high-resolution 3-D mapping of CCM lesions in mouse brains. Using this method, we found loss of Ccm1 or Ccm2 in neonatal endothelium confers CCM lesions in the mouse hindbrain with similar total volume and number. This quantitative approach also demonstrated a rescue of CCM lesions with simultaneous deletion of one allele of Mekk3. This method would enhance the value of the established mouse models to study the molecular basis and potential therapies for CCM and other cerebrovascular diseases. | |
dc.format | Electronic-eCollection | |
dc.language | eng | |
dc.publisher | PUBLIC LIBRARY SCIENCE | |
dc.relation.ispartof | PLoS One | |
dc.relation.isbasedon | 10.1371/journal.pone.0160833 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject.classification | General Science & Technology | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Animals, Newborn | |
dc.subject.mesh | Disease Models, Animal | |
dc.subject.mesh | Female | |
dc.subject.mesh | Gene Deletion | |
dc.subject.mesh | Heterozygote | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Intellectual Disability | |
dc.subject.mesh | MAP Kinase Kinase Kinase 3 | |
dc.subject.mesh | Male | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Mice, Knockout | |
dc.subject.mesh | Microfilament Proteins | |
dc.subject.mesh | Micrognathism | |
dc.subject.mesh | Ribs | |
dc.subject.mesh | X-Ray Microtomography | |
dc.subject.mesh | Ribs | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Animals, Newborn | |
dc.subject.mesh | Mice, Knockout | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Micrognathism | |
dc.subject.mesh | Disease Models, Animal | |
dc.subject.mesh | Microfilament Proteins | |
dc.subject.mesh | MAP Kinase Kinase Kinase 3 | |
dc.subject.mesh | Gene Deletion | |
dc.subject.mesh | Heterozygote | |
dc.subject.mesh | Female | |
dc.subject.mesh | Male | |
dc.subject.mesh | X-Ray Microtomography | |
dc.subject.mesh | Intellectual Disability | |
dc.title | Micro-CT Imaging Reveals Mekk3 Heterozygosity Prevents Cerebral Cavernous Malformations in Ccm2-Deficient Mice. | |
dc.type | Journal Article | |
utslib.citation.volume | 11 | |
utslib.location.activity | United States | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
utslib.copyright.status | open_access | * |
dc.date.updated | 2022-08-13T06:39:43Z | |
pubs.issue | 8 | |
pubs.publication-status | Published online | |
pubs.volume | 11 | |
utslib.citation.issue | 8 |
Abstract:
Mutations in CCM1 (aka KRIT1), CCM2, or CCM3 (aka PDCD10) gene cause cerebral cavernous malformation in humans. Mouse models of CCM disease have been established by deleting Ccm genes in postnatal animals. These mouse models provide invaluable tools to investigate molecular mechanism and therapeutic approaches for CCM disease. However, the full value of these animal models is limited by the lack of an accurate and quantitative method to assess lesion burden and progression. In the present study we have established a refined and detailed contrast enhanced X-ray micro-CT method to measure CCM lesion burden in mouse brains. As this study utilized a voxel dimension of 9.5μm (leading to a minimum feature size of approximately 25μm), it is therefore sufficient to measure CCM lesion volume and number globally and accurately, and provide high-resolution 3-D mapping of CCM lesions in mouse brains. Using this method, we found loss of Ccm1 or Ccm2 in neonatal endothelium confers CCM lesions in the mouse hindbrain with similar total volume and number. This quantitative approach also demonstrated a rescue of CCM lesions with simultaneous deletion of one allele of Mekk3. This method would enhance the value of the established mouse models to study the molecular basis and potential therapies for CCM and other cerebrovascular diseases.
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