Characterization of Pathology in Transgenic Mice Over-Expressing Human Genomic and cDNA Tau Transgenes

doi:10.1006/nbdi.1999.0279

Neurobiology of Disease

Volume 7, Issue 2, April 2000, Pages 87-98

https://doi.org/10.1006/nbdi.1999.0279 Get rights and content

Abstract

To examine the normal cellular function of tau and its role in pathogenesis, we have created transgenic mice that overexpress a tau transgene derived from a human PAC that contains the coding sequence, intronic regions, and regulatory regions of the human gene. All six isoforms of human tau are represented in the transgenic mouse brain at the mRNA and protein level and the human tau is distributed in neurites and at synapses, but is absent from cell bodies. A comparison between the genomic tau mice and mice that overexpress a tau cDNA transgene shows that overall, the distribution of tau is similar in the two lines, but human tau is located in the somatodendritic compartment of many neurons in the cDNA mice. Tau-immunoreactive axonal swellings were found in the spinal cords of the cDNA mice, which correlated with a hind-limb abnormality, whereas neuropathology was essentially normal in the genomic mice up to 8 months of age.

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Regular ArticleCharacterization of Pathology in Transgenic Mice Over-Expressing Human Genomic and cDNA Tau Transgenes

Abstract

Int. J. Dev. Neurosci.

Am. J. Pathol.

FEBS Lett.

Neuron

J. Biol. Chem.

FEBS Lett.

FEBS Lett.

Trends Neurosci.

Structure and novel exons of the human tau gene

Biochemistry

Embryonic lethal abnormal vision-like RNA-binding proteins regulate neurite outgrowth and tau expression in PC12 cells

J. Neurosci.

A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads

Acta Neuropathol. (Berl)

Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements

Proc. Natl. Acad. Sci. USA

Expression of separate isoforms of human tau protein: Correlation with the tau pattern in brain and effects on tubulin polymerization

EMBO J.

Epitope mapping of monoclonal antibodies to the paired helical filaments of Alzheimer's disease: Identification of phosphorylation sites in tau protein

Biochem. J.

Tau gene mutation in familial progressive subcortical gliosis

Nat. Med.

Somatodendritic localization and hyperphosphorylation of tau protein in transgenic mice expressing the longest human brain tau isoform

EMBO J.

Regular Article
Characterization of Pathology in Transgenic Mice Over-Expressing Human Genomic and cDNA Tau Transgenes