Clinical–electrophysiological correlation of tremor and myoclonus in a kindred with the N279K tau mutation

The tau mutation in the golden (Syrian) hamster is a single gene mutation that drastically affects the speed of the circadian clock, in such a way that homozygous mutants have an endogenous circadian period of 20 h (compared with 24 h for wild-type hamsters). While studying the circadian system of tau-mutant hamsters during the past 25 years, several authors have noted an apparent relationship between circadian period and body size in these animals. This study, based on 181 hamsters from 24 litters, confirmed previous observations that a shorter circadian period is associated with smaller body size, documented a sex difference in this association, and evaluated several mechanisms that might explain the phenomenon (such as different organ sizes, body composition, and metabolic rate). The obtained evidence suggests that the reduced body size of short-period hamsters is likely a pleiotropic effect of the tau allele (an allele of the casein kinase 1 epsilon gene) rather than a consequence of the shortened circadian period.

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Tau Mutation

Encyclopedia of Neuroscience ◽

10.1007/978-3-540-29678-2_5908 ◽

2008 ◽

pp. 4031-4031

Keyword(s):

Tau Mutation

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Sites of phosphorylation in tau and factors affecting their regulation

Biochemical Society Symposium ◽

10.1042/bss0670073 ◽

2001 ◽

Vol 67 ◽

pp. 73-80 ◽

Cited By ~ 60

Author(s):

Brian H. Anderton ◽

Joanna Betts ◽

Walter P. Blackstock ◽

Jean-Pierre Brion ◽

Sara Chapman ◽

...

Keyword(s):

Glycogen Synthase ◽

Principal Component ◽

Paired Helical Filaments ◽

Glycogen Synthase Kinase 3 ◽

P38 Kinase ◽

Factors Affecting ◽

Extracellular Signal ◽

Mitogen Activated Protein ◽

Tau Mutation

The microtubule-associated protein, tau, is the principal component of paired helical filaments (PHFs) in Alzheimer's disease. PHF-tau is highly phosphorylated and a total of 25 sites of phosphorylation have so far been identified. Many of these sites are serine or threonine residues that are immediately followed in the sequence by proline residues, and hence are candidate phosphorylation sites for proline-directed kinases. In vitro, glycogen synthase kinase-3 (GSK-3), extracellular signal-related kinase-1 and -2, and mitogen-activated protein kinases, p38 kinase and c-jun N-terminal kinase, all phosphorylate many of these sites, although with different efficiencies for particular sites. Phosphorylation studies in transfected cells and neurons show that GSK-3 phosphorylates tau more extensively than do these other proline-directed kinases. Mutations in tau have been shown to affect in vitro phosphorylation of tau by GSK-3. The Arg406-->Trp (R406W) tau mutation also affects tau phosphorylation in cells.

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