Deprivation of Muscleblind-Like Proteins Causes Deficits in Cortical Neuron Distribution and Morphological Changes in Dendritic Spines and Postsynaptic Densities
Myotonic dystrophy (Dystrophia Myotonica; DM) is the most common adult-onset muscular dystrophy and its brain symptoms seriously affect patients' quality of life. It is caused by extended (CTG) expansions at 3'-UTR of gene (DM type 1, DM1) or (CCTG) repeats in the intron 1 of gene (DM type...
Saved in:
Published in | Frontiers in neuroanatomy Vol. 13; p. 75 |
---|---|
Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Research Foundation
30.07.2019
Frontiers Media S.A |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Myotonic dystrophy (Dystrophia Myotonica; DM) is the most common adult-onset muscular dystrophy and its brain symptoms seriously affect patients' quality of life. It is caused by extended (CTG)
expansions at 3'-UTR of
gene (DM type 1, DM1) or (CCTG)
repeats in the intron 1 of
gene (DM type 2, DM2) and the sequestration of Muscleblind-like (MBNL) family proteins by transcribed (CUG)
RNA hairpin is the main pathogenic mechanism for DM. The MBNL proteins are splicing factors regulating posttranscriptional RNA during development. Previously,
knockout (KO) mouse lines showed molecular and phenotypic evidence that recapitulate DM brains, however, detailed morphological study has not yet been accomplished. In our studies, control (
;
;
),
conditional KO (2KO,
;
;
) and
double KO (DKO,
;
;
) mice were generated by crossing three individual lines. Immunohistochemistry for evaluating density and distribution of cortical neurons; Golgi staining for depicting the dendrites/dendritic spines; and electron microscopy for analyzing postsynaptic ultrastructure were performed. We found distributional defects in cortical neurons, reduction in dendritic complexity, immature dendritic spines and alterations of postsynaptic densities (PSDs) in the mutants. In conclusion, loss of function of Mbnl1/2 caused fundamental defects affecting neuronal distribution, dendritic morphology and postsynaptic architectures that are reminiscent of predominantly immature and fetal phenotypes in DM patients. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Nicolas Heck, Université Pierre et Marie Curie, France Reviewed by: Richard Belvindrah, Sorbonne Universités, France; Mario Gomes-Pereira, Institut National de la Santé et de la Recherche Médicale (INSERM), France |
ISSN: | 1662-5129 1662-5129 |
DOI: | 10.3389/fnana.2019.00075 |