PMID- 11193141
OWN - NLM
STAT- MEDLINE
DCOM- 20010208
LR  - 20190616
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 920
DP  - 2000
TI  - In vivo analysis of wild-type and FTDP-17 tau transgenic mice.
PG  - 126-33
AB  - Mutations in the coding and intronic regions of the tau gene cause frontotemporal 
      dementia and parkinsonism linked to chromosome 17 (FTDP-17). Some of these 
      mutations lead to an overproduction of tau isoforms with four microtubule-binding 
      repeats, followed by the development of fibrillary lesions and selective cell 
      death. In order to analyze the development of these neurofibrillary lesions in 
      transgenic mice, the longest four-repeat human brain tau isoform was expressed 
      under control of two different neuron-specific promoters. In a first model, 
      utilizing the human Thy1 promoter, transgenic tau was hyperphosphorylated and 
      abnormally localized to cell bodies and dendrites. In a second model, which made 
      use of a human Thy1.2 expression vector, transgenic expression levels were much 
      higher, and an additional phenotype was observed: Large numbers of pathologically 
      enlarged axons containing neurofilament- and tau-immunoreactive spheroids were 
      present, especially in spinal cord. Signs of Wallerian degeneration and 
      neurogenic muscle atrophy were observed. Behaviorally, transgenic mice showed 
      signs of muscle weakness. Our data show that overexpression of human four-repeat 
      tau in itself is sufficient to lead to nerve cell dysfunction and amyotrophy. We 
      have now extended our initial studies by introducing exonic mutations including 
      G2t 2V and PS01L into the tau gene in order to achieve a more advanced FTDP-17 
      associated phenotype.
FAU - Gotz, J
AU  - Gotz J
AD  - Department of Psychiatry Research, University of Zurich, August Forel Str. 1, 
      8008 Zurich, Switzerland. goetz@bli.unizh.ch
FAU - Barmettler, R
AU  - Barmettler R
FAU - Ferrari, A
AU  - Ferrari A
FAU - Goedert, M
AU  - Goedert M
FAU - Probst, A
AU  - Probst A
FAU - Nitsch, R M
AU  - Nitsch RM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Protein Isoforms)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Animals
MH  - Brain/metabolism/pathology
MH  - Chromosomes, Human, Pair 17
MH  - Dementia/*genetics
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Parkinson Disease/*genetics
MH  - Phosphorylation
MH  - Protein Isoforms/genetics
MH  - tau Proteins/*genetics
RF  - 24
EDAT- 2001/02/24 12:00
MHDA- 2001/03/03 10:01
CRDT- 2001/02/24 12:00
PHST- 2001/02/24 12:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2001/02/24 12:00 [entrez]
AID - 10.1111/j.1749-6632.2000.tb06914.x [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2000;920:126-33. doi: 10.1111/j.1749-6632.2000.tb06914.x.