PMID- 10932182
OWN - NLM
STAT- MEDLINE
DCOM- 20000828
LR  - 20071114
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 25
IP  - 4
DP  - 2000 Aug
TI  - Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice 
      expressing mutant (P301L) tau protein.
PG  - 402-5
AB  - Neurofibrillary tangles (NFT) composed of the microtubule-associated protein tau 
      are prominent in Alzheimer disease (AD), Pick disease, progressive supranuclear 
      palsy (PSP) and corticobasal degeneration (CBD). Mutations in the gene (Mtapt) 
      encoding tau protein cause frontotemporal dementia and parkinsonism linked to 
      chromosome 17 (FTDP-17), thereby proving that tau dysfunction can directly result 
      in neurodegeneration. Expression of human tau containing the most common FTDP-17 
      mutation (P301L) results in motor and behavioural deficits in transgenic mice, 
      with age- and gene-dose-dependent development of NFT. This phenotype occurred as 
      early as 6.5 months in hemizygous and 4.5 months in homozygous animals. NFT and 
      Pick-body-like neuronal lesions occurred in the amygdala, septal nuclei, 
      pre-optic nuclei, hypothalamus, midbrain, pons, medulla, deep cerebellar nuclei 
      and spinal cord, with tau-immunoreactive pre-tangles in the cortex, hippocampus 
      and basal ganglia. Areas with the most NFT had reactive gliosis. Spinal cord had 
      axonal spheroids, anterior horn cell loss and axonal degeneration in anterior 
      spinal roots. We also saw peripheral neuropathy and skeletal muscle with 
      neurogenic atrophy. Brain and spinal cord contained insoluble tau that 
      co-migrated with insoluble tau from AD and FTDP-17 brains. The phenotype of mice 
      expressing P301L mutant tau mimics features of human tauopathies and provides a 
      model for investigating the pathogenesis of diseases with NFT.
FAU - Lewis, J
AU  - Lewis J
AD  - Mayo Clinic Jacksonville, Jacksonville, Florida, USA.
FAU - McGowan, E
AU  - McGowan E
FAU - Rockwood, J
AU  - Rockwood J
FAU - Melrose, H
AU  - Melrose H
FAU - Nacharaju, P
AU  - Nacharaju P
FAU - Van Slegtenhorst, M
AU  - Van Slegtenhorst M
FAU - Gwinn-Hardy, K
AU  - Gwinn-Hardy K
FAU - Paul Murphy, M
AU  - Paul Murphy M
FAU - Baker, M
AU  - Baker M
FAU - Yu, X
AU  - Yu X
FAU - Duff, K
AU  - Duff K
FAU - Hardy, J
AU  - Hardy J
FAU - Corral, A
AU  - Corral A
FAU - Lin, W L
AU  - Lin WL
FAU - Yen, S H
AU  - Yen SH
FAU - Dickson, D W
AU  - Dickson DW
FAU - Davies, P
AU  - Davies P
FAU - Hutton, M
AU  - Hutton M
LA  - eng
GR  - P01/PHS HHS/United States
GR  - R01/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (tau Proteins)
SB  - IM
EIN - Nat Genet 2000 Sep;26(1):127
MH  - Amino Acid Substitution
MH  - Animals
MH  - Brachial Plexus Neuritis/*genetics
MH  - Brain Stem/metabolism/pathology/ultrastructure
MH  - Cell Count
MH  - Gene Expression
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Mice, Transgenic
MH  - Movement Disorders/*genetics
MH  - Muscle, Skeletal/metabolism/pathology/ultrastructure
MH  - Mutation
MH  - Neurofibrillary Tangles/*genetics
MH  - Neurons/pathology/ultrastructure
MH  - Spinal Cord/metabolism/pathology/ultrastructure
MH  - tau Proteins/*genetics
EDAT- 2000/08/10 11:00
MHDA- 2000/09/02 11:01
CRDT- 2000/08/10 11:00
PHST- 2000/08/10 11:00 [pubmed]
PHST- 2000/09/02 11:01 [medline]
PHST- 2000/08/10 11:00 [entrez]
AID - 10.1038/78078 [doi]
PST - ppublish
SO  - Nat Genet. 2000 Aug;25(4):402-5. doi: 10.1038/78078.