DESCRIPTION:

QTL associated with tau phosphorylation. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (86279489)

LABEL:

QTL-Tauph-Mouse-Chr 16

SCORE TYPE:

Binary

DATE ADDED:

2012-04-02

DATE UPDATED:

2024-10-22

SPECIES:

URI:

http://www.informatics.jax.org/searches/accession_report.cgi?id=MGI:2664867

AUTHORS:

Brich J, Shie FS, Howell BW, Li R, Tus K, Wakeland EK, Jin LW, Mumby M, Churchill G, Herz J, Cooper JA

TITLE:

Genetic modulation of tau phosphorylation in the mouse.

JOURNAL:

The Journal of neuroscience : the official journal of the Society for Neuroscience Jan 2003, Vol 23, pp. 187-92

ABSTRACT:

The axonal microtubule stabilizing protein tau is hyperphosphorylated in several neurodegenerative conditions, including Alzheimer\'s disease, yet the genes that regulate tau phosphorylation are largely unknown. Disabled-1 (Dab1) is a cytoplasmic adapter protein that interacts with apolipoprotein E (ApoE) receptors and controls neuronal positioning during embryonic brain development. We have investigated the role of Dab1 in tau phosphorylation. We found that wild-type Dab1, but not a mutant lacking tyrosine phosphorylation sites, protects mice from the hyperphosphorylation of tau. However, the absence of Dab1 is not sufficient to cause tau hyperphosphorylation, because hyperphosphorylation is manifested only when Dab1 is mutated in specific mouse strain backgrounds. Tau hyperphosphorylation correlates with early death in susceptible mouse strains, and it occurs in the neurons of the hippocampus and dentate gyrus. By quantitative trait locus (QTL) analysis of Dab1-deficient mice 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 Alzheimer\'s disease. Our findings suggest that Dab1 gene disruption sensitizes mice to tau hyperphosphorylation contingent on specific haplotypes that are linked to Alzheimer\'s disease loci. Dab1 mutant mice provide an animal model for studying the relationships between ApoE receptors, tau hyperphosphorylation, and Alzheimer\'s disease. PUBMED: 12514215
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