Gene expression profiling of the tau mutant (P301L) transgenic mouse brain

To provide a global analysis of the influence of Tau neuropathology at molecular level, we used cDNA arrays representing 8832 genes to determine the mRNA expression profile in transgenic mice expressing the most common frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) Tau mutation (P301L) (Nat. Genet. (2000) 402). Genes whose expression is associated with development of neurofibrillary tangles and neuron loss in P301L mice with motor and behavioral deficits were identified. The data suggest that a major mechanism underlying P301LTau neurodegeneration primarily involved altered expression of genes contributing to inhibition of apoptosis and intracellular transport. We propose that the expression of mutated P301L may lead to select altered expression of genes which may cause neurodegeneration in FTDP-17.

[1]  M. Shichiri,et al.  Induction of max by adrenomedullin and calcitonin gene-related peptide antagonizes endothelial apoptosis. , 1999, Molecular endocrinology.

[2]  R. Nitsch,et al.  Tau Filament Formation in Transgenic Mice Expressing P301L Tau* , 2001, The Journal of Biological Chemistry.

[3]  B. Robertson,et al.  Interferon-γ receptors are expressed at synapses in the rat superficial dorsal horn and lateral spinal nucleus , 1998, Journal of neurocytology.

[4]  E. Mandelkow,et al.  Overexpression of Tau Protein Inhibits Kinesin-dependent Trafficking of Vesicles, Mitochondria, and Endoplasmic Reticulum: Implications for Alzheimer's Disease , 1998, The Journal of cell biology.

[5]  R. Suzuki,et al.  Molecular cloning of a novel CC chemokine, interleukin‐11 receptor α‐locus chemokine (ILC), which is located on chromosome 9p13 and a potential homologue of a CC chemokine encoded by molluscum contagiosum virus , 1999, FEBS letters.

[6]  Wen-Lang Lin,et al.  Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein , 2000, Nature Genetics.

[7]  M. Gunn,et al.  Gene Duplications at the Chemokine Locus on Mouse Chromosome 4: Multiple Strain-Specific Haplotypes and the Deletion of Secondary Lymphoid-Organ Chemokine and EBI-1 Ligand Chemokine Genes in the plt Mutation1 , 2001, The Journal of Immunology.

[8]  N. Cairns,et al.  Neuronal apoptosis inhibitory protein (NAIP)-like immunoreactivity in brains of adult patients with Down syndrome. , 1999, Journal of neural transmission. Supplementum.

[9]  Sunjong Kwon,et al.  RNA trafficking in myelinating cells , 1998, Current Opinion in Neurobiology.

[10]  H. Lipshitz,et al.  RNA localization in development. , 1998, Annual review of biochemistry.

[11]  N. Hecht,et al.  The suppression of testis-brain RNA binding protein and kinesin heavy chain disrupts mRNA sorting in dendrites. , 1999, Journal of cell science.

[12]  W. Saxton,et al.  A function for kinesin I in the posterior transport of oskar mRNA and Staufen protein. , 2000, Science.

[13]  M. Kiebler,et al.  Molecular Insights into mRNA Transport and Local Translation in the Mammalian Nervous System , 2000, Neuron.

[14]  A. Lawen,et al.  Rapamycin inhibits didemnin B‐induced apoptosis in human HL‐60 cells: Evidence for the possible involvement of FK506‐binding protein 25 , 1999, Immunology and cell biology.

[15]  H. Nishimatsu,et al.  Adrenomedullin and nitric oxide inhibit human endothelial cell apoptosis via a cyclic GMP-independent mechanism. , 2000, Hypertension.

[16]  D. Vaux,et al.  Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. Kiebler,et al.  The Mammalian Staufen Protein Localizes to the Somatodendritic Domain of Cultured Hippocampal Neurons: Implications for Its Involvement in mRNA Transport , 1999, The Journal of Neuroscience.

[18]  D. Dickson,et al.  Neurodegenerative diseases with cytoskeletal pathology: A biochemical classification , 1997, Annals of neurology.