Genetic modulation of tau phosphorylation in the XXXX .

@entity6970 @entity19 @entity3072 @entity195 @entity669 @entity47141 @entity204
The axonal microtubule stabilizing protein tau is hyperphosphorylated in several neurodegenerative conditions, including @entity195 , yet the genes that regulate tau phosphorylation are largely unknown. @entity47141 ( @entity47141 ) is a cytoplasmic adapter protein that interacts with @entity6970 ( @entity6970 ) receptors and controls neuronal positioning during embryonic brain development. We have investigated the role of @entity47141 in tau phosphorylation. We found that wild-type @entity47141 , but not a mutant lacking @entity669 phosphorylation sites, protects @entity19 from the hyperphosphorylation of tau. However, the absence of @entity47141 is not sufficient to cause @entity3072 , because hyperphosphorylation is manifested only when @entity47141 is mutated in specific @entity19 backgrounds. Tau hyperphosphorylation correlates with @entity204 in susceptible @entity19 strains, and it occurs in the neurons of the hippocampus and dentate gyrus. By quantitative trait locus (QTL) analysis of @entity47141 -deficient @entity19 on a hybrid strain background, we uncovered one significant and three suggestive chromosomal loci that modulate tau phosphorylation. Two of these QTL regions contain genes that are defective in early onset @entity195 . Our findings suggest that @entity47141 gene disruption sensitizes @entity19 to @entity3072 contingent on specific haplotypes that are linked to @entity195 loci. @entity47141 mutant @entity19 provide an animal model for studying the relationships between @entity6970 receptors, @entity3072 , and @entity195 .
