Document Detail


Abnormal nuclear envelope in the cerebellar Purkinje cells and impaired motor learning in DYT11 myoclonus-dystonia mouse models.
MedLine Citation:
PMID:  22040906     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonia. DYT11 M-D is caused by mutations in SGCE which codes for ɛ-sarcoglycan. SGCE is maternally imprinted and paternally expressed. Abnormal nuclear envelope has been reported in mouse models of DYT1 generalized torsion dystonia. However, it is not known whether similar alterations occur in DYT11 M-D. We developed a mouse model of DYT11 M-D using paternally inherited Sgce heterozygous knockout (Sgce KO) mice and reported that they had myoclonus and motor coordination and learning deficits in the beam-walking test. However, the specific brain regions that contribute to these phenotypes have not been identified. Since ɛ-sarcoglycan is highly expressed in the cerebellar Purkinje cells, here we examined the nuclear envelope in these cells using a transmission electron microscope and found that they are abnormal in Sgce KO mice. Our results put DYT11 M-D in a growing family of nuclear envelopathies. To analyze the effect of loss of ɛ-sarcoglycan function in the cerebellar Purkinje cells, we produced paternally inherited cerebellar Purkinje cell-specific Sgce conditional knockout (Sgce pKO) mice. Sgce pKO mice showed motor learning deficits, while they did not show abnormal nuclear envelope in the cerebellar Purkinje cells, robust motor deficits, or myoclonus. The results suggest that ɛ-sarcoglycan in the cerebellar Purkinje cells contributes to the motor learning, while loss of ɛ-sarcoglycan in other brain regions may contribute to nuclear envelope abnormality, myoclonus and motor coordination deficits.
Authors:
Fumiaki Yokoi; Mai T Dang; Guang Yang; Jindong Li; Atbin Doroodchi; Tong Zhou; Yuqing Li
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-21
Journal Detail:
Title:  Behavioural brain research     Volume:  227     ISSN:  1872-7549     ISO Abbreviation:  Behav. Brain Res.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2011-12-19     Completed Date:  2012-04-23     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  8004872     Medline TA:  Behav Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  12-20     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cerebellum / pathology*
Disease Models, Animal
Dystonia Musculorum Deformans / complications
Dystonic Disorders / complications*,  genetics,  pathology*
Exploratory Behavior / physiology
Extracellular Matrix Proteins / genetics
Learning Disorders / etiology*
Locomotion / genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Electron, Transmission
Motor Activity
Nuclear Envelope / pathology*,  ultrastructure
Posture
Protein-Lysine 6-Oxidase / genetics
Purkinje Cells / pathology*,  ultrastructure
Rotarod Performance Test
Sarcoglycans / deficiency
Stereotyped Behavior / physiology
Grant Support
ID/Acronym/Agency:
NS37409/NS/NINDS NIH HHS; NS47466/NS/NINDS NIH HHS; NS47692/NS/NINDS NIH HHS; NS54246/NS/NINDS NIH HHS; NS57098/NS/NINDS NIH HHS; NS65273/NS/NINDS NIH HHS; NS72876/NS/NINDS NIH HHS; NS74423/NS/NINDS NIH HHS; P30 NS047466/NS/NINDS NIH HHS; P30 NS047466-07/NS/NINDS NIH HHS; P30 NS057098/NS/NINDS NIH HHS; P30 NS057098-05/NS/NINDS NIH HHS; P50 NS037409/NS/NINDS NIH HHS; P50 NS037409-10A1/NS/NINDS NIH HHS; R01 NS054246/NS/NINDS NIH HHS; R01 NS054246-04/NS/NINDS NIH HHS; R01 NS054246-05/NS/NINDS NIH HHS; R03 NS074423/NS/NINDS NIH HHS; R03 NS074423-01/NS/NINDS NIH HHS; R21 NS047692/NS/NINDS NIH HHS; R21 NS047692-03/NS/NINDS NIH HHS; R21 NS065273/NS/NINDS NIH HHS; R21 NS065273-03/NS/NINDS NIH HHS; R21 NS072872/NS/NINDS NIH HHS; R21 NS072872-03/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Extracellular Matrix Proteins; 0/Sarcoglycans; 149137-54-2/Lox protein, mouse; EC 1.4.3.13/Protein-Lysine 6-Oxidase
Comments/Corrections

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