PMID- 12417659
OWN - NLM
STAT- MEDLINE
DCOM- 20021125
LR  - 20220309
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 22
IP  - 21
DP  - 2002 Nov 1
TI  - Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice 
      expressing human P301S tau protein.
PG  - 9340-51
AB  - The identification of mutations in the Tau gene in frontotemporal dementia and 
      parkinsonism linked to chromosome 17 (FTDP-17) has made it possible to express 
      human tau protein with pathogenic mutations in transgenic animals. Here we report 
      on the production and characterization of a line of mice transgenic for the 383 
      aa isoform of human tau with the P301S mutation. At 5-6 months of age, homozygous 
      animals from this line developed a neurological phenotype dominated by a severe 
      paraparesis. According to light microscopy, many nerve cells in brain and spinal 
      cord were strongly immunoreactive for hyperphosphorylated tau. According to 
      electron microscopy, abundant filaments made of hyperphosphorylated tau protein 
      were present. The majority of filaments resembled the half-twisted ribbons 
      described previously in cases of FTDP-17, with a minority of filaments resembling 
      the paired helical filaments of Alzheimer's disease. Sarkosyl-insoluble tau from 
      brains and spinal cords of transgenic mice ran as a hyperphosphorylated 64 kDa 
      band, the same apparent molecular mass as that of the 383 aa tau isoform in the 
      human tauopathies. Perchloric acid-soluble tau was also phosphorylated at many 
      sites, with the notable exception of serine 214. In the spinal cord, 
      neurodegeneration was present, as indicated by a 49% reduction in the number of 
      motor neurons. No evidence for apoptosis was obtained, despite the extensive 
      colocalization of hyperphosphorylated tau protein with activated MAP kinase 
      family members. The latter may be involved in the hyperphosphorylation of tau.
FAU - Allen, Bridget
AU  - Allen B
AD  - Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, 
      United Kingdom.
FAU - Ingram, Esther
AU  - Ingram E
FAU - Takao, Masaki
AU  - Takao M
FAU - Smith, Michael J
AU  - Smith MJ
FAU - Jakes, Ross
AU  - Jakes R
FAU - Virdee, Kanwar
AU  - Virdee K
FAU - Yoshida, Hirotaka
AU  - Yoshida H
FAU - Holzer, Max
AU  - Holzer M
FAU - Craxton, Molly
AU  - Craxton M
FAU - Emson, Piers C
AU  - Emson PC
FAU - Atzori, Cristiana
AU  - Atzori C
FAU - Migheli, Antonio
AU  - Migheli A
FAU - Crowther, R Anthony
AU  - Crowther RA
FAU - Ghetti, Bernardino
AU  - Ghetti B
FAU - Spillantini, Maria Grazia
AU  - Spillantini MG
FAU - Goedert, Michel
AU  - Goedert M
LA  - eng
GR  - P30 AG010133/AG/NIA NIH HHS/United States
GR  - P30 AG10133/AG/NIA NIH HHS/United States
GR  - R01 NS14426/NS/NINDS NIH 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  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Benzothiazoles)
RN  - 0 (Thiazoles)
RN  - 0 (tau Proteins)
RN  - 2390-54-7 (thioflavin T)
RN  - 632GS99618 (sarkosyl)
RN  - Z711V88R5F (Sarcosine)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - Apoptosis
MH  - Benzothiazoles
MH  - Brain/pathology/physiopathology
MH  - Brain Chemistry
MH  - Cell Count
MH  - Disease Models, Animal
MH  - Homozygote
MH  - Humans
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Transgenic
MH  - Motor Neurons/pathology
MH  - Neurodegenerative Diseases/complications/*pathology/*physiopathology
MH  - Paraparesis/etiology/physiopathology
MH  - Phenotype
MH  - Phosphorylation
MH  - Sarcosine/*analogs & derivatives/chemistry
MH  - Solubility
MH  - Spinal Cord/chemistry/pathology/physiopathology
MH  - Thiazoles
MH  - tau Proteins/chemistry/*genetics/*metabolism/ultrastructure
PMC - PMC6758022
EDAT- 2002/11/06 04:00
MHDA- 2002/11/26 04:00
PMCR- 2003/05/01
CRDT- 2002/11/06 04:00
PHST- 2002/11/06 04:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/11/06 04:00 [entrez]
PHST- 2003/05/01 00:00 [pmc-release]
AID - 22/21/9340 [pii]
AID - 6982 [pii]
AID - 10.1523/JNEUROSCI.22-21-09340.2002 [doi]
PST - ppublish
SO  - J Neurosci. 2002 Nov 1;22(21):9340-51. doi: 10.1523/JNEUROSCI.22-21-09340.2002.