MRI analysis of cerebellar and vestibular developmental phenotypes in Gbx2 conditional knockout mice
Purpose Our aim in this study was to apply three‐dimensional MRI methods to analyze early postnatal morphological phenotypes in a Gbx2 conditional knockout (Gbx2‐CKO) mouse that has variable midline deletions in the central cerebellum, reminiscent of many human cerebellar hypoplasia syndromes. Metho...
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| Published in: | Magnetic resonance in medicine Vol. 70; no. 6; pp. 1707 - 1717 |
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| Main Authors: | , , , , , , |
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01-12-2013
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| Abstract | Purpose
Our aim in this study was to apply three‐dimensional MRI methods to analyze early postnatal morphological phenotypes in a Gbx2 conditional knockout (Gbx2‐CKO) mouse that has variable midline deletions in the central cerebellum, reminiscent of many human cerebellar hypoplasia syndromes.
Methods
In vivo three‐dimensional manganese‐enhanced MRI at 100‐µm isotropic resolution was used to visualize mouse brains between postnatal days 3 and 11, when cerebellum morphology undergoes dramatic changes. Deformation‐based morphometry and volumetric analysis of manganese‐enhanced MRI images were used to, respectively, detect and quantify morphological phenotypes in Gbx2‐CKO mice. Ex vivo micro‐MRI was performed after perfusion‐fixation with supplemented gadolinium for higher resolution (50‐µm) analysis.
Results
In vivo manganese‐enhanced MRI and deformation‐based morphometry correctly identified known cerebellar defects in Gbx2‐CKO mice, and novel phenotypes were discovered in the deep cerebellar nuclei and the vestibulo‐cerebellum, both validated using histology. Ex vivo micro‐MRI revealed subtle phenotypes in both the vestibulo‐cerebellum and the vestibulo‐cochlear organ, providing an interesting example of complementary phenotypes in a sensory organ and its associated brain region.
Conclusion
These results show the potential of three‐dimensional MRI for detecting and analyzing developmental defects in mouse models of neurodevelopmental diseases. Magn Reson Med 70:1707–1717, 2013. © 2013 Wiley Periodicals, Inc. |
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| AbstractList | PURPOSEOur aim in this study was to apply three-dimensional MRI methods to analyze early postnatal morphological phenotypes in a Gbx2 conditional knockout (Gbx2-CKO) mouse that has variable midline deletions in the central cerebellum, reminiscent of many human cerebellar hypoplasia syndromes. METHODSIn vivo three-dimensional manganese-enhanced MRI at 100-µm isotropic resolution was used to visualize mouse brains between postnatal days 3 and 11, when cerebellum morphology undergoes dramatic changes. Deformation-based morphometry and volumetric analysis of manganese-enhanced MRI images were used to, respectively, detect and quantify morphological phenotypes in Gbx2-CKO mice. Ex vivo micro-MRI was performed after perfusion-fixation with supplemented gadolinium for higher resolution (50-µm) analysis. RESULTSIn vivo manganese-enhanced MRI and deformation-based morphometry correctly identified known cerebellar defects in Gbx2-CKO mice, and novel phenotypes were discovered in the deep cerebellar nuclei and the vestibulo-cerebellum, both validated using histology. Ex vivo micro-MRI revealed subtle phenotypes in both the vestibulo-cerebellum and the vestibulo-cochlear organ, providing an interesting example of complementary phenotypes in a sensory organ and its associated brain region. CONCLUSIONThese results show the potential of three-dimensional MRI for detecting and analyzing developmental defects in mouse models of neurodevelopmental diseases. Purpose Our aim in this study was to apply three-dimensional MRI methods to analyze early postnatal morphological phenotypes in a Gbx2 conditional knockout (Gbx2-CKO) mouse that has variable midline deletions in the central cerebellum, reminiscent of many human cerebellar hypoplasia syndromes. Methods In vivo three-dimensional manganese-enhanced MRI at 100-µm isotropic resolution was used to visualize mouse brains between postnatal days 3 and 11, when cerebellum morphology undergoes dramatic changes. Deformation-based morphometry and volumetric analysis of manganese-enhanced MRI images were used to, respectively, detect and quantify morphological phenotypes in Gbx2-CKO mice. Ex vivo micro-MRI was performed after perfusion-fixation with supplemented gadolinium for higher resolution (50-µm) analysis. Results In vivo manganese-enhanced MRI and deformation-based morphometry correctly identified known cerebellar defects in Gbx2-CKO mice, and novel phenotypes were discovered in the deep cerebellar nuclei and the vestibulo-cerebellum, both validated using histology. Ex vivo micro-MRI revealed subtle phenotypes in both the vestibulo-cerebellum and the vestibulo-cochlear organ, providing an interesting example of complementary phenotypes in a sensory organ and its associated brain region. Conclusion These results show the potential of three-dimensional MRI for detecting and analyzing developmental defects in mouse models of neurodevelopmental diseases. Magn Reson Med 70:1707-1717, 2013. © 2013 Wiley Periodicals, Inc. [PUBLICATION ABSTRACT] Purpose Our aim in this study was to apply three-dimensional MRI methods to analyze early postnatal morphological phenotypes in a Gbx2 conditional knockout (Gbx2-CKO) mouse that has variable midline deletions in the central cerebellum, reminiscent of many human cerebellar hypoplasia syndromes. Methods In vivo three-dimensional manganese-enhanced MRI at 100- mu m isotropic resolution was used to visualize mouse brains between postnatal days 3 and 11, when cerebellum morphology undergoes dramatic changes. Deformation-based morphometry and volumetric analysis of manganese-enhanced MRI images were used to, respectively, detect and quantify morphological phenotypes in Gbx2-CKO mice. Ex vivo micro-MRI was performed after perfusion-fixation with supplemented gadolinium for higher resolution (50- mu m) analysis. Results In vivo manganese-enhanced MRI and deformation-based morphometry correctly identified known cerebellar defects in Gbx2-CKO mice, and novel phenotypes were discovered in the deep cerebellar nuclei and the vestibulo-cerebellum, both validated using histology. Ex vivo micro-MRI revealed subtle phenotypes in both the vestibulo-cerebellum and the vestibulo-cochlear organ, providing an interesting example of complementary phenotypes in a sensory organ and its associated brain region. Conclusion These results show the potential of three-dimensional MRI for detecting and analyzing developmental defects in mouse models of neurodevelopmental diseases. Magn Reson Med 70:1707-1717, 2013. [copy 2013 Wiley Periodicals, Inc. Purpose Our aim in this study was to apply three‐dimensional MRI methods to analyze early postnatal morphological phenotypes in a Gbx2 conditional knockout (Gbx2‐CKO) mouse that has variable midline deletions in the central cerebellum, reminiscent of many human cerebellar hypoplasia syndromes. Methods In vivo three‐dimensional manganese‐enhanced MRI at 100‐µm isotropic resolution was used to visualize mouse brains between postnatal days 3 and 11, when cerebellum morphology undergoes dramatic changes. Deformation‐based morphometry and volumetric analysis of manganese‐enhanced MRI images were used to, respectively, detect and quantify morphological phenotypes in Gbx2‐CKO mice. Ex vivo micro‐MRI was performed after perfusion‐fixation with supplemented gadolinium for higher resolution (50‐µm) analysis. Results In vivo manganese‐enhanced MRI and deformation‐based morphometry correctly identified known cerebellar defects in Gbx2‐CKO mice, and novel phenotypes were discovered in the deep cerebellar nuclei and the vestibulo‐cerebellum, both validated using histology. Ex vivo micro‐MRI revealed subtle phenotypes in both the vestibulo‐cerebellum and the vestibulo‐cochlear organ, providing an interesting example of complementary phenotypes in a sensory organ and its associated brain region. Conclusion These results show the potential of three‐dimensional MRI for detecting and analyzing developmental defects in mouse models of neurodevelopmental diseases. Magn Reson Med 70:1707–1717, 2013. © 2013 Wiley Periodicals, Inc. Our aim in this study was to apply three-dimensional MRI methods to analyze early postnatal morphological phenotypes in a Gbx2 conditional knockout (Gbx2-CKO) mouse that has variable midline deletions in the central cerebellum, reminiscent of many human cerebellar hypoplasia syndromes. In vivo three-dimensional manganese-enhanced MRI at 100-µm isotropic resolution was used to visualize mouse brains between postnatal days 3 and 11, when cerebellum morphology undergoes dramatic changes. Deformation-based morphometry and volumetric analysis of manganese-enhanced MRI images were used to, respectively, detect and quantify morphological phenotypes in Gbx2-CKO mice. Ex vivo micro-MRI was performed after perfusion-fixation with supplemented gadolinium for higher resolution (50-µm) analysis. In vivo manganese-enhanced MRI and deformation-based morphometry correctly identified known cerebellar defects in Gbx2-CKO mice, and novel phenotypes were discovered in the deep cerebellar nuclei and the vestibulo-cerebellum, both validated using histology. Ex vivo micro-MRI revealed subtle phenotypes in both the vestibulo-cerebellum and the vestibulo-cochlear organ, providing an interesting example of complementary phenotypes in a sensory organ and its associated brain region. These results show the potential of three-dimensional MRI for detecting and analyzing developmental defects in mouse models of neurodevelopmental diseases. |
| Author | Lerch, Jason P. Turnbull, Daniel H. Joyner, Alexandra L. Nieman, Brian J. Houston, Edward J. Bartelle, Benjamin B. Szulc, Kamila U. |
| AuthorAffiliation | 5 Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada 6 Developmental Biology Program, Sloan-Kettering Institute, New York, NY, USA 2 Biomedical Imaging, New York, NY, USA 3 Molecular Biophysics Graduate Programs, New York, NY, USA 1 Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine 4 Departments of Radiology and Pathology, New York University School of Medicine, New York, NY, USA |
| AuthorAffiliation_xml | – name: 6 Developmental Biology Program, Sloan-Kettering Institute, New York, NY, USA – name: 1 Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine – name: 2 Biomedical Imaging, New York, NY, USA – name: 4 Departments of Radiology and Pathology, New York University School of Medicine, New York, NY, USA – name: 3 Molecular Biophysics Graduate Programs, New York, NY, USA – name: 5 Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada |
| Author_xml | – sequence: 1 givenname: Kamila U. surname: Szulc fullname: Szulc, Kamila U. organization: Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA – sequence: 2 givenname: Brian J. surname: Nieman fullname: Nieman, Brian J. organization: Mouse Imaging Centre, Hospital for Sick Children, Ontario, Toronto, Canada – sequence: 3 givenname: Edward J. surname: Houston fullname: Houston, Edward J. organization: Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA – sequence: 4 givenname: Benjamin B. surname: Bartelle fullname: Bartelle, Benjamin B. organization: Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA – sequence: 5 givenname: Jason P. surname: Lerch fullname: Lerch, Jason P. organization: Mouse Imaging Centre, Hospital for Sick Children, Ontario, Toronto, Canada – sequence: 6 givenname: Alexandra L. surname: Joyner fullname: Joyner, Alexandra L. organization: Developmental Biology Program, Sloan-Kettering Institute, New York, New York, USA – sequence: 7 givenname: Daniel H. surname: Turnbull fullname: Turnbull, Daniel H. email: daniel.turnbull@med.nyu.edu organization: Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23400959$$D View this record in MEDLINE/PubMed |
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| Keywords | brain development mid-hindbrain manganese-enhanced MRI (MEMRI) cerebellum gastrulation brain homeobox 2 gene (Gbx2) vestibulo-cochlear organ |
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Our aim in this study was to apply three‐dimensional MRI methods to analyze early postnatal morphological phenotypes in a Gbx2 conditional knockout... Our aim in this study was to apply three-dimensional MRI methods to analyze early postnatal morphological phenotypes in a Gbx2 conditional knockout (Gbx2-CKO)... Purpose Our aim in this study was to apply three-dimensional MRI methods to analyze early postnatal morphological phenotypes in a Gbx2 conditional knockout... PURPOSEOur aim in this study was to apply three-dimensional MRI methods to analyze early postnatal morphological phenotypes in a Gbx2 conditional knockout... |
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| SubjectTerms | Animal models Animals Animals, Newborn brain development cerebellum Cerebellum - abnormalities Cerebellum - growth & development Cerebellum - pathology Cerebellum - physiopathology Developmental Disabilities - genetics Developmental Disabilities - pathology Developmental Disabilities - physiopathology gastrulation brain homeobox 2 gene (Gbx2) Homeodomain Proteins - genetics Magnetic Resonance Imaging - methods manganese-enhanced MRI (MEMRI) Mice Mice, Knockout mid-hindbrain Nervous System Malformations - genetics Nervous System Malformations - pathology Nervous System Malformations - physiopathology Phenotype Reproducibility of Results Sensitivity and Specificity Vestibule, Labyrinth - abnormalities Vestibule, Labyrinth - growth & development Vestibule, Labyrinth - pathology vestibulo-cochlear organ |
| Title | MRI analysis of cerebellar and vestibular developmental phenotypes in Gbx2 conditional knockout mice |
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