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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.

Original publication

DOI

10.1002/mrm.24597

Type

Journal article

Journal

Magn Reson Med

Publication Date

12/2013

Volume

70

Pages

1707 - 1717

Keywords

brain development, cerebellum, gastrulation brain homeobox 2 gene (Gbx2), manganese-enhanced MRI (MEMRI), mid-hindbrain, vestibulo-cochlear organ, Animals, Animals, Newborn, Cerebellum, Developmental Disabilities, Homeodomain Proteins, Magnetic Resonance Imaging, Mice, Mice, Knockout, Nervous System Malformations, Phenotype, Reproducibility of Results, Sensitivity and Specificity, Vestibule, Labyrinth