Gait dynamics in trisomic mice: quantitative neurological traits of Down syndrome

Hampton, Thomas G.; Stasko, Melissa R.; Kale, Ajit; Amende, Ivo; Costa, Alberto C. S.

doi:10.1016/j.physbeh.2004.04.006

Cited by 102 publications

(97 citation statements)

References 39 publications

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“…A total of 41 mice were used (hMT1, nine transgenic, four nontransgenic; hMT2, eight transgenic, seven nontransgenic; hWT, seven transgenic, six nontransgenic). Digital images were collected and analyzed using a DigiGait Imaging System (Mouse Specifics, Boston, MA) (Hampton et al, 2004). Four variables were considered (stride length, paw angle, absolute paw angle, and stance/swing ratio) for each paw at two running speeds (20 and 40 cm/s).…”

Section: Methodsmentioning

confidence: 99%

Impaired Motor Learning in Mice Expressing TorsinA with the DYT1 Dystonia Mutation

Sharma¹,

Baxter²,

Petravicz³

et al. 2005

J. Neurosci.

133

150

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Primary early-onset generalized dystonia is an autosomal dominant disorder caused by a deletion (⌬GAG) in the DYT1 gene encoding torsinA. The gene defect has incomplete penetrance, with ϳ30% of carriers developing clinically evident dystonia. We describe lines of transgenic mice that express either human mutant torsinA (hMT) or human wild-type (hWT) torsinA. All mice demonstrated moderately increased levels of torsinA in the brain by Western blot analysis and normal subcellular distribution of torsinA in neurons by confocal microscopy. No animals had dystonic features. However, mice overexpressing hMT, but not hWT, torsinA displayed a reduced ability to learn motor skills in an accelerating rotarod paradigm. This pattern resembles the impaired motor sequence learning demonstrated in human nonmanifesting carriers of the ⌬GAG mutation. Open-field testing showed no differences in spontaneous activity between transgenic mice and their nontransgenic littermates, indicating that mice overexpressing hMT torsinA did not develop overtly abnormal motor behavior. Together, these data suggest that these transgenic mice provide a useful model of the ⌬GAG carrier state that can be used to probe genetic and environmental factors that can trigger the dystonic state.

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Section: Methodsmentioning

confidence: 99%

Impaired Motor Learning in Mice Expressing TorsinA with the DYT1 Dystonia Mutation

Sharma¹,

Baxter²,

Petravicz³

et al. 2005

J. Neurosci.

133

150

View full text Add to dashboard Cite

show abstract

“…The DigiGait imaging system (Mouse Specifics) was used for gait analyses as previously described (Hampton et al, 2004).…”

Section: Behavioral Testsmentioning

confidence: 99%

Striatal Expression of a Calmodulin Fragment Improved Motor Function, Weight Loss, and Neuropathology in the R6/2 Mouse Model of Huntington's Disease

Dai¹,

Dudek²,

Li³

et al. 2009

J. Neurosci.

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Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, caused by a polyglutamine expansion in the huntingtin protein (htt). Increasing evidence suggests that transglutaminase (TGase) plays a critical role in the pathophysiology of HD possibly by stabilizing monomeric, polymeric and aggregated htt. We previously reported that in HEK293 and SH-SY5Y cells expression of a calmodulin (CaM)-fragment, consisting of amino acids 76-121 of CaM, decreased binding of CaM to mutant htt, TGase-modified htt and cytotoxicity associated with mutant htt and normalized intracellular calcium release. In this study, an adeno-associated virus (AAV) that expresses the CaM-fragment was injected into the striatum of HD transgenic R6/2 mice. The CaM-fragment significantly reduced body weight loss and improved motor function as indicated by improved rotarod performance, longer stride length, lower stride frequency, fewer low mobility bouts and longer travel distance than HD controls. A small but insignificant increase in survival was observed in R6/2 mice with CaM-fragment expression. Immunoprecipitation studies show that expression of the CaM-fragment reduced TGase-modified htt in the striatum of R6/2 mice. The percentage of htt-positive nuclei and the size of intranuclear htt aggregates were reduced by the CaM-fragment without striatal volume changes. The effects of CaM-fragment appear to be selective, as activity of another CaM-dependent enzyme, CaM-dependent kinase II, was not altered. Moreover, inhibition of TGase-modified htt was substrate-specific since overall TGase activity in the striatum was not altered by treatment with the CaM-fragment. Together, these results suggest that disrupting CaM-htt interaction may provide a new therapeutic strategy for HD.

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“…Imaging and analysis software automatically quantifies spatial and temporal indices of gait in walking or running animals. Additional details have been published previously [13][14][15]. The experimental design was similar to the locomotor activity measurements except that only one measurement session was conducted at each of the two age points.…”

Section: Gait Dynamicsmentioning

confidence: 99%

MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels

Oien

Osterhaus

Latif

et al. 2008

Free Radical Biology and Medicine

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Oxidative stress can cause methionine oxidation that has been implicated in various proteins malfunctions, if not adequately reduced by the methionine sulfoxide reductase system. Recent evidence has found oxidized methionine residues in neurodegenerative conditions. Previously, we have described elevated levels of brain pathologies and an abnormal walking pattern in the methionine sulfoxide reductase A knockout (MsrA −/− ) mouse. Here we show that MsrA −/− mice have compromised complex task learning capabilities relative to wild-type mice. Likewise, MsrA −/− mice exhibit lower locomotor activity and altered gait that exacerbated with age. Furthermore, MsrA −/− mice were less responsive to amphetamine treatment. Consequently, brain dopamine levels were determined. Surprisingly, relative to wild-type mice, MsrA −/− brains contained significantly higher levels of dopamine up to 12 months of age, while lower level of dopamine was observed at 16 months of age. Moreover, striatal regions of MsrA −/− mice showed an increase of dopamine release parallel to observed dopamine levels. Similarly, the expression pattern of tyrosine hydroxylase activating protein correlated with the age-dependent dopamine levels. Thus, it is suggested that dopamine regulation and signaling pathway are impaired in MsrA −/− mice, which may contribute to their abnormal bio-behavior. These observations may be relevant to age-related neurological diseases associated with oxidative stress.

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Gait dynamics in trisomic mice: quantitative neurological traits of Down syndrome

Cited by 102 publications

References 39 publications

Impaired Motor Learning in Mice Expressing TorsinA with the DYT1 Dystonia Mutation

Impaired Motor Learning in Mice Expressing TorsinA with the DYT1 Dystonia Mutation

Striatal Expression of a Calmodulin Fragment Improved Motor Function, Weight Loss, and Neuropathology in the R6/2 Mouse Model of Huntington's Disease

MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels

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