RGD Reference Report - Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP.

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Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP.
Authors:	Andreassen, O A Ferrante, R J Dedeoglu, A Albers, D W Klivenyi, P Carlson, E J Epstein, C J Beal, M F
Citation:	Andreassen OA, etal., Exp Neurol. 2001 Jan;167(1):189-95. doi: 10.1006/exnr.2000.7525.
RGD ID:	13464352
Pubmed:	PMID:11161607 (View Abstract at PubMed)
DOI:	DOI:10.1006/exnr.2000.7525 (Journal Full-text)
There is substantial evidence implicating mitochondrial dysfunction and free radical generation as major mechanisms of neuronal death in neurodegenerative diseases. The major free radical scavenging enzyme in mitochondria is manganese superoxide dismutase (SOD2). In the present study we investigated the susceptibility of mice with a partial deficiency of SOD2 to the neurotoxins 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), 3-nitropropionic acid (3-NP), and malonate, which are commonly used animal models of Parkinson's and Huntington's disease. Heterozygous SOD2 knockout (SOD2(+/-)) mice showed no evidence of neuropathological or behavioral abnormalities at 2-4 months of age. Compared to littermate wild-type mice, mice with partial SOD2 deficiency showed increased vulnerability to dopamine depletion after systemic MPTP treatment and significantly larger striatal lesions produced by both 3-NP and malonate. SOD2(+/-) mice also showed an increased production of "hydroxyl" radicals after malonate injection measured with the salicylate hydroxyl radical trapping method. These results provide further evidence that reactive oxygen species play an important role in the neurotoxicity of MPTP, malonate, and 3-NP. These findings show that a subclinical deficiency in a free radical scavenging enzyme may act in concert with environmental toxins to produce selective neurodegeneration.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Huntington's disease	susceptibility	ISO	Sod2 (Mus musculus)	13464352; 13464352		RGD
Huntington's disease	susceptibility	IMP		13464352		RGD
Parkinson's disease	susceptibility	ISO	Sod2 (Mus musculus)	13464352; 13464352		RGD
Parkinson's disease	susceptibility	IMP		13464352		RGD

Objects Annotated

Genes (Rattus norvegicus)

Sod2 (superoxide dismutase 2)

Genes (Mus musculus)

Sod2 (superoxide dismutase 2, mitochondrial)

Genes (Homo sapiens)

SOD2 (superoxide dismutase 2)

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Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP.