Deprivation of Muscleblind-Like Proteins Causes Deficits in Cortical Neuron Distribution and Morphological Changes in Dendritic Spines and Postsynaptic Densities

Kuang Yung Lee*, Ho Ching Chang, Carol Seah, Li Jen Lee

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

20 引文 斯高帕斯(Scopus)

摘要

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)n expansions at 3′-UTR of DMPK gene (DM type 1, DM1) or (CCTG)n repeats in the intron 1 of CNBP gene (DM type 2, DM2) and the sequestration of Muscleblind-like (MBNL) family proteins by transcribed (CUG)n RNA hairpin is the main pathogenic mechanism for DM. The MBNL proteins are splicing factors regulating posttranscriptional RNA during development. Previously, Mbnl 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 (Mbnl1+/+; Mbnl2cond/cond; Nestin-Cre−/−), Mbnl2 conditional KO (2KO, Mbnl1+/+; Mbnl2cond/cond; Nestin-Cre+/−) and Mbnl1/2 double KO (DKO, Mbnl1ΔE3/ΔE3; Mbnl2cond/cond; Nestin-Cre+/−) 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.

原文英語
文章編號75
期刊Frontiers in Neuroanatomy
13
DOIs
出版狀態已出版 - 30 07 2019

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© Copyright © 2019 Lee, Chang, Seah and Lee.

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