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Progressive Behavioral Deficits in DJ-1 Deficient Mice are Associated with Normal Nigrostriatal Function

Loss-of-function mutations in the DJ-1 gene account for an autosomal recessive form of Parkinson’s disease (PD). To investigate the physiological functions of DJ-1 in vivo, we generated DJ-1 knockout (DJ-1(-/-)) mice. Younger (< 1year) DJ-1 (-/-) mice were hypoactive and had mild gait abnormaliti...

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Huvudupphovsmän: Chandran, Jayanth S., Lin, Xian, Zapata, Agustin, Höke, Ahmet, Shimoji, Mika, Moore, Shonagh O’Leary, Galloway, Matthew P., Laird, Fiona M., Wong, Philip C., Price, Donald L., Bailey, Kathleen R., Crawley, Jacqueline N, Shippenberg, Toni, Cai, Huaibin
Materialtyp: Artikel
Språk:English
Publicerad: 2007
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Länkar:https://ncbi.nlm.nih.gov/pmc/articles/PMC2271119/
https://ncbi.nlm.nih.gov/pubmed/18187333
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1016/j.nbd.2007.11.011
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spelling pubmed-22711192009-03-01 Progressive Behavioral Deficits in DJ-1 Deficient Mice are Associated with Normal Nigrostriatal Function Chandran, Jayanth S. Lin, Xian Zapata, Agustin Höke, Ahmet Shimoji, Mika Moore, Shonagh O’Leary Galloway, Matthew P. Laird, Fiona M. Wong, Philip C. Price, Donald L. Bailey, Kathleen R. Crawley, Jacqueline N Shippenberg, Toni Cai, Huaibin Neurobiol Dis Article Loss-of-function mutations in the DJ-1 gene account for an autosomal recessive form of Parkinson’s disease (PD). To investigate the physiological functions of DJ-1 in vivo, we generated DJ-1 knockout (DJ-1(-/-)) mice. Younger (< 1year) DJ-1 (-/-) mice were hypoactive and had mild gait abnormalities. Older DJ-1(-/-), however, showed decreased bodyweight and grip strength, and more severe gait irregularities compared to wild-type littermates. The basal level of extracellular dopamine, evoked dopamine release and dopamine receptor D2 sensitivity appeared normal in the striatum of DJ-1(-/-) mice, which was consistent with similar results between DJ-1(-/-) and controls in behavioral paradigms specific for the dopaminergic system. An examination of spinal cord, nerve and muscle tissues failed to identify any pathological changes that were consistent with the noted motor deficits. Taken together, our findings suggest that loss of DJ-1 leads to progressive behavioral changes without significant alterations in nigrostriatal dopaminergic and spinal motor systems. 2007-12-04 2008-03 /pmc/articles/PMC2271119/ /pubmed/18187333 http://dx.doi.org/10.1016/j.nbd.2007.11.011 Text en
institution US National Library of Medicine
collection PubMed Central
language English
format Article
topic Article
spellingShingle Article
Chandran, Jayanth S.
Lin, Xian
Zapata, Agustin
Höke, Ahmet
Shimoji, Mika
Moore, Shonagh O’Leary
Galloway, Matthew P.
Laird, Fiona M.
Wong, Philip C.
Price, Donald L.
Bailey, Kathleen R.
Crawley, Jacqueline N
Shippenberg, Toni
Cai, Huaibin
Progressive Behavioral Deficits in DJ-1 Deficient Mice are Associated with Normal Nigrostriatal Function
description Loss-of-function mutations in the DJ-1 gene account for an autosomal recessive form of Parkinson’s disease (PD). To investigate the physiological functions of DJ-1 in vivo, we generated DJ-1 knockout (DJ-1(-/-)) mice. Younger (< 1year) DJ-1 (-/-) mice were hypoactive and had mild gait abnormalities. Older DJ-1(-/-), however, showed decreased bodyweight and grip strength, and more severe gait irregularities compared to wild-type littermates. The basal level of extracellular dopamine, evoked dopamine release and dopamine receptor D2 sensitivity appeared normal in the striatum of DJ-1(-/-) mice, which was consistent with similar results between DJ-1(-/-) and controls in behavioral paradigms specific for the dopaminergic system. An examination of spinal cord, nerve and muscle tissues failed to identify any pathological changes that were consistent with the noted motor deficits. Taken together, our findings suggest that loss of DJ-1 leads to progressive behavioral changes without significant alterations in nigrostriatal dopaminergic and spinal motor systems.
author Chandran, Jayanth S.
Lin, Xian
Zapata, Agustin
Höke, Ahmet
Shimoji, Mika
Moore, Shonagh O’Leary
Galloway, Matthew P.
Laird, Fiona M.
Wong, Philip C.
Price, Donald L.
Bailey, Kathleen R.
Crawley, Jacqueline N
Shippenberg, Toni
Cai, Huaibin
author_facet Chandran, Jayanth S.
Lin, Xian
Zapata, Agustin
Höke, Ahmet
Shimoji, Mika
Moore, Shonagh O’Leary
Galloway, Matthew P.
Laird, Fiona M.
Wong, Philip C.
Price, Donald L.
Bailey, Kathleen R.
Crawley, Jacqueline N
Shippenberg, Toni
Cai, Huaibin
author_sort Chandran, Jayanth S.
title Progressive Behavioral Deficits in DJ-1 Deficient Mice are Associated with Normal Nigrostriatal Function
title_short Progressive Behavioral Deficits in DJ-1 Deficient Mice are Associated with Normal Nigrostriatal Function
title_full Progressive Behavioral Deficits in DJ-1 Deficient Mice are Associated with Normal Nigrostriatal Function
title_fullStr Progressive Behavioral Deficits in DJ-1 Deficient Mice are Associated with Normal Nigrostriatal Function
title_full_unstemmed Progressive Behavioral Deficits in DJ-1 Deficient Mice are Associated with Normal Nigrostriatal Function
title_sort progressive behavioral deficits in dj-1 deficient mice are associated with normal nigrostriatal function
publishDate 2007
url https://ncbi.nlm.nih.gov/pmc/articles/PMC2271119/
https://ncbi.nlm.nih.gov/pubmed/18187333
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1016/j.nbd.2007.11.011
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