MRI analysis of cerebellar and vestibular developmental phenotypes in Gbx2 conditional knockout mice

Magn Reson Med. 2013 Dec;70(6):1707-17. doi: 10.1002/mrm.24597. Epub 2013 Feb 7.


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.

Keywords: brain development; cerebellum; gastrulation brain homeobox 2 gene (Gbx2); manganese-enhanced MRI (MEMRI); mid-hindbrain; vestibulo-cochlear organ.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Cerebellum / abnormalities*
  • Cerebellum / growth & development
  • Cerebellum / pathology*
  • Cerebellum / physiopathology
  • Developmental Disabilities / genetics
  • Developmental Disabilities / pathology
  • Developmental Disabilities / physiopathology
  • Homeodomain Proteins / genetics*
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Knockout
  • 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*


  • Gbx2 protein, mouse
  • Homeodomain Proteins

Supplementary concepts

  • Cerebellar Hypoplasia