MRI Analysis of Cerebellar and Vestibular Developmental Phenotypes in Gbx2 Conditional Knockout Mice

作者：Szulc Kamila U; Nieman Brian J; Houston Edward J; Bartelle Benjamin B; Lerch Jason P; Joyner Alexandra L; Turnbull Daniel H^*

来源：Magnetic Resonance in Medicine, 2013, 70(6): 1707-1717.

DOI：10.1002/mrm.24597

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

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-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.
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. Magn Reson Med 70:1707-1717, 2013.

• 出版日期2013-12