title: MRI analysis of cerebellar and vestibular developmental phenotypes in Gbx2 conditional knockout mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  These results show the potential of three-dimensional MRI for detecting and analyzing developmental defects in mouse models of neurodevelopmental diseases.
authors: Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA; Biomedical Imaging Program, New York University School of Medicine, New York, New York, USA.
authors: Kamila U
authors: KU
authors: Szulc
authors: Brian J
authors: BJ
authors: Nieman
authors: Edward J
authors: EJ
authors: Houston
authors: Benjamin B
authors: BB
authors: Bartelle
authors: Jason P
authors: JP
authors: Lerch
authors: Alexandra L
authors: AL
authors: Joyner
authors: Daniel H
authors: DH
authors: Turnbull
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000002:abnormalities* / Q000254:growth & development / Q000473:pathology* / Q000503:physiopathology; D002658:Developmental Disabilities / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D018398:Homeodomain Proteins / Q000235:genetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D009421:Nervous System Malformations / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D010641:Phenotype; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014722:Vestibule, Labyrinth / Q000002:abnormalities* / Q000254:growth & development / Q000473:pathology*
chemical_list: C513182:Gbx2 protein, mouse; D018398:Homeodomain Proteins
keywords: brain development; cerebellum; gastrulation brain homeobox 2 gene (Gbx2); manganese-enhanced MRI (MEMRI); mid-hindbrain; vestibulo-cochlear organ
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