MRI analysis of cerebellar and vestibular developmental phenotypes in Gbx2 conditional knockout mice
Article first published online: 7 FEB 2013
Copyright © 2013 Wiley Periodicals, Inc.
Magnetic Resonance in Medicine
Volume 70, Issue 6, pages 1707–1717, December 2013
How to Cite
Szulc, K. U., Nieman, B. J., Houston, E. J., Bartelle, B. B., Lerch, J. P., Joyner, A. L. and Turnbull, D. H. (2013), MRI analysis of cerebellar and vestibular developmental phenotypes in Gbx2 conditional knockout mice. Magn Reson Med, 70: 1707–1717. doi: 10.1002/mrm.24597
- Issue published online: 18 NOV 2013
- Article first published online: 7 FEB 2013
- Manuscript Accepted: 21 NOV 2012
- Manuscript Revised: 20 NOV 2012
- Manuscript Received: 31 AUG 2012
- NIH . Grant Number: RO1 N5038461
- brain development;
- gastrulation brain homeobox 2 gene (Gbx2);
- manganese-enhanced MRI (MEMRI);
- vestibulo-cochlear organ
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. Magn Reson Med 70:1707–1717, 2013. © 2013 Wiley Periodicals, Inc.