MRI Features in a Rat Model of H-ABC Tubulinopathy

Tubulinopathies are a group of recently described diseases characterized by mutations in the tubulin genes. Mutations in TUBB4A produce diseases such as dystonia 4 (DYT4) and hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC), which are clinically diagnosed by magnetic resonanc...

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Published inFrontiers in neuroscience Vol. 14; p. 555
Main Authors Garduno-Robles, Angeles, Alata, Milvia, Piazza, Valeria, Cortes, Carmen, Eguibar, Jose R., Pantano, Sergio, Hernandez, Victor H.
Format Journal Article
LanguageEnglish
Published Lausanne Frontiers Research Foundation 03.06.2020
Frontiers Media S.A
Subjects
Animal models
Ataxia
Atrophy
Basal ganglia
Brain research
Cerebellum
Disease
Dystonia
Epilepsy
Genetic analysis
Genetic engineering
Genotype & phenotype
H-ABC
hypo/demyelination
Light microscopy
Magnetic resonance imaging
Microscopy
MRI
Mutation
Myelin
Nervous system
Neurodegeneration
Neuroimaging
Neuroscience
Optical density
optical microscopy
Paralysis
Pathology
Putamen
Spinal cord
Substantia alba
taiep
Tremor
Tubulin
tubulinopathies
United States > US
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Summary:Tubulinopathies are a group of recently described diseases characterized by mutations in the tubulin genes. Mutations in TUBB4A produce diseases such as dystonia 4 (DYT4) and hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC), which are clinically diagnosed by magnetic resonance imaging (MRI). We propose the taiep rat as the first animal model for tubulinopathies. The spontaneous mutant suffers from a syndrome related to a central leukodistrophy and characterized by tremor, ataxia, immobility, epilepsy and paralysis. The clinical signs presented by these rats and the morphological changes we found by our longitudinal MRI study are similar to those of patients with mutations in TUBB4A. The diffuse atrophy we found in brain, cerebellum and spinal cord is related to the changes detectable in many human tubulinopathies and in particular in H-ABC patients, where myelin degeneration at the level of putamen and cerebellum is a clinical trademark of the disease. We performed Tubb4a exon analysis to corroborate the genetic defect and formulated hypotheses about the effect of aminoacid 302 change on protein physiology. Optical microscopy of taiep rat cerebella and spinal cord confirmed the optical density loss in white matter associated with myelin loss, despite the persistence of neural fibers.
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Edited by: Sadayuki Hashioka, Shimane University, Japan
This article was submitted to Neurodegeneration, a section of the journal Frontiers in Neuroscience
These authors have contributed equally to this work
Reviewed by: Rodolfo Gabriel Gatto, University of Illinois at Chicago, United States; Gianluca Serafini, San Martino Hospital (IRCCS), Italy
ISSN:1662-453X
1662-4548
1662-453X
DOI:10.3389/fnins.2020.00555