Impairments in motor coordination without major changes in cerebellar plasticity in the Tc1 mouse model of Down syndrome
Author(s)
Type
Journal Article
Abstract
Down syndrome (DS) is a genetic disorder arising from the presence of a third copy of human chromosome
21 (Hsa21). Recently, O’Doherty
et al
. [An aneuploid mouse strain carrying human chromosome 21 with Down
syndrome phenotypes.
Science
309 (2005) 2033 – 2037] generated a
trans
-species aneuploid mouse line (Tc1)
that carries an almost complete Hsa21. The Tc1 mouse is the most complete animal model for DS currently
available. Tc1 mice show many features that relate to human DS, including alterations in memory, synaptic
plasticity, cerebellar neuronal number, heart devel
opment and mandible size. Because motor deficits are
one of the most frequently occurring features of DS, we have undertaken a detailed analysis of motor beha-
viour in cerebellum-dependent learning tasks that require high motor coordination and balance. In addition,
basic electrophysiological properties of cerebellar circuitry and synaptic plasticity have been investigated.
Our results reveal that, compared with controls, Tc1 mice exhibit a higher spontaneous locomotor activity,
a reduced ability to habituate to their environments, a different gait and major deficits on several measures
of motor coordination and balance in the rota rod and static rod tests. Moreover, cerebellar long-term
depression is essentially normal in Tc1 mice, with only a slight difference in time course. Our observations
provide further evidence that support the validity of the Tc1 mouse as a model for DS, which will help us to
provide insights into the causal factors responsible for motor deficits observed in persons with DS.
21 (Hsa21). Recently, O’Doherty
et al
. [An aneuploid mouse strain carrying human chromosome 21 with Down
syndrome phenotypes.
Science
309 (2005) 2033 – 2037] generated a
trans
-species aneuploid mouse line (Tc1)
that carries an almost complete Hsa21. The Tc1 mouse is the most complete animal model for DS currently
available. Tc1 mice show many features that relate to human DS, including alterations in memory, synaptic
plasticity, cerebellar neuronal number, heart devel
opment and mandible size. Because motor deficits are
one of the most frequently occurring features of DS, we have undertaken a detailed analysis of motor beha-
viour in cerebellum-dependent learning tasks that require high motor coordination and balance. In addition,
basic electrophysiological properties of cerebellar circuitry and synaptic plasticity have been investigated.
Our results reveal that, compared with controls, Tc1 mice exhibit a higher spontaneous locomotor activity,
a reduced ability to habituate to their environments, a different gait and major deficits on several measures
of motor coordination and balance in the rota rod and static rod tests. Moreover, cerebellar long-term
depression is essentially normal in Tc1 mice, with only a slight difference in time course. Our observations
provide further evidence that support the validity of the Tc1 mouse as a model for DS, which will help us to
provide insights into the causal factors responsible for motor deficits observed in persons with DS.
Date Issued
2009-01-29
Date Acceptance
2009-01-27
Citation
HUMAN MOLECULAR GENETICS, 2009, 18 (8), pp.1449-1463
ISSN
0964-6906
Publisher
Oxford University Press
Start Page
1449
End Page
1463
Journal / Book Title
HUMAN MOLECULAR GENETICS
Volume
18
Issue
8
Copyright Statement
© 2009 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.or
g/
licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original wor
kis
properly cited.
g/
licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original wor
kis
properly cited.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000264889800008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Genetics & Heredity
LONG-TERM POTENTIATION
CLIMBING FIBER INNERVATION
MICE LACKING MGLUR1
HIGH-RESOLUTION MRI
PURKINJE-CELLS
TS65DN MOUSE
SYNAPTIC PLASTICITY
MULTIPLE INNERVATION
RAT CEREBELLUM
BEHAVIORAL ABNORMALITIES
Publication Status
Published