References
Query Results -- Details
MGI Accession ID: MGI:4360462
J Number: J:152957
Other Accession IDs:
Title: Elimination of GD3 synthase improves memory and reduces amyloid-beta plaque load in transgenic mice.
Authors: Bernardo A; Harrison FE; McCord M; Zhao J; Bruchey A; Davies SS; Jackson Roberts L nd; Mathews PM; Matsuoka Y; Ariga T; Yu RK; Thompson R; McDonald MP
Journal: Neurobiol Aging
Volume: 30
Issue: 11
Date: 2009 Nov
Year: 2009
Pages: 1777-91
Review Status: Peer Reviewed
Abstract:
Gangliosides have been shown to be necessary for beta-amyloid (Abeta) binding and aggregation. GD3 synthase (GD3S) is responsible for biosynthesis of the b- and c-series gangliosides, including two of the four major brain gangliosides. We examined Abeta-ganglioside interactions in neural tissue from mice lacking the gene coding for GD3S (St8sia1), and in a double-transgenic (APP/PSEN1) mouse model of Alzheimer's disease cross-bred with GD3S-/- mice. In primary neurons and astrocytes lacking GD3S, Abeta-induced cell death and Abeta aggregation were inhibited. Like GD3S-/- and APP/PSEN1 double-transgenic mice, APP/PSEN1/GD3S-/- 'triple-mutant' mice are indistinguishable from wild-type mice on casual examination. APP/PSEN1 double-transgenics exhibit robust impairments on a number of reference-memory tasks. In contrast, APP/PSEN1/GD3S-/- triple-mutant mice performed as well as wild-type control and GD3S-/- mice. Consistent with the behavioral improvements, both aggregated and unaggregated Abeta and associated neuropathology were almost completely eliminated in triple-mutant mice. These results suggest that GD3 synthase may be a novel therapeutic target to combat the cognitive deficits, amyloid plaque formation, and neurodegeneration that afflict Alzheimer's patients.
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