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Impairments in motor coordination without major changes in cerebellar plasticity in the Tc1 mouse model of Down syndrome.

Galante M, Jani H, Vanes L, Daniel H, Fisher EM, Tybulewicz VL, Bliss TV, Morice E - Hum. Mol. Genet. (2009)

Bottom Line: Because motor deficits are one of the most frequently occurring features of DS, we have undertaken a detailed analysis of motor behaviour 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 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Pharmacologie de la Synapse, CNRS UMR 8619, Université Paris-Sud, 91405 Orsay Cedex, France.

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 development and mandible size. Because motor deficits are one of the most frequently occurring features of DS, we have undertaken a detailed analysis of motor behaviour 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.

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Grip force measurement in WT (white bars) and Tc1 (black bars) mice. The results represent the mean grip force (g) immediately prior to the animal releasing its grasp from the grid (see Methods). No difference was observed between Tc1 and WT mice either for four paws or for front legs, indicating normal muscles strength in Tc1 mice. Values represent means ± S.E.M.
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DDP055F4: Grip force measurement in WT (white bars) and Tc1 (black bars) mice. The results represent the mean grip force (g) immediately prior to the animal releasing its grasp from the grid (see Methods). No difference was observed between Tc1 and WT mice either for four paws or for front legs, indicating normal muscles strength in Tc1 mice. Values represent means ± S.E.M.

Mentions: In order to test if poor performances of Tc1 mice on the rota rod were due to abnormal muscle strength, they were assessed with the grip test. Our results revealed no significant difference, either for the front legs (F1,26=2.13, P = 0.16) or for the four legs (F1,26=0.55, P = 0.46), in the grip forces produced by Tc1 and WT mice (Fig. 4). These data demonstrate that Tc1 mice have no impairment in muscle strength and their impaired rota rod motor learning task is not due to differences in grip capability.


Impairments in motor coordination without major changes in cerebellar plasticity in the Tc1 mouse model of Down syndrome.

Galante M, Jani H, Vanes L, Daniel H, Fisher EM, Tybulewicz VL, Bliss TV, Morice E - Hum. Mol. Genet. (2009)

Grip force measurement in WT (white bars) and Tc1 (black bars) mice. The results represent the mean grip force (g) immediately prior to the animal releasing its grasp from the grid (see Methods). No difference was observed between Tc1 and WT mice either for four paws or for front legs, indicating normal muscles strength in Tc1 mice. Values represent means ± S.E.M.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2664148&req=5

DDP055F4: Grip force measurement in WT (white bars) and Tc1 (black bars) mice. The results represent the mean grip force (g) immediately prior to the animal releasing its grasp from the grid (see Methods). No difference was observed between Tc1 and WT mice either for four paws or for front legs, indicating normal muscles strength in Tc1 mice. Values represent means ± S.E.M.
Mentions: In order to test if poor performances of Tc1 mice on the rota rod were due to abnormal muscle strength, they were assessed with the grip test. Our results revealed no significant difference, either for the front legs (F1,26=2.13, P = 0.16) or for the four legs (F1,26=0.55, P = 0.46), in the grip forces produced by Tc1 and WT mice (Fig. 4). These data demonstrate that Tc1 mice have no impairment in muscle strength and their impaired rota rod motor learning task is not due to differences in grip capability.

Bottom Line: Because motor deficits are one of the most frequently occurring features of DS, we have undertaken a detailed analysis of motor behaviour 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 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Pharmacologie de la Synapse, CNRS UMR 8619, Université Paris-Sud, 91405 Orsay Cedex, France.

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 development and mandible size. Because motor deficits are one of the most frequently occurring features of DS, we have undertaken a detailed analysis of motor behaviour 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.

Show MeSH
Related in: MedlinePlus