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

To provide a global analysis of the influence of Tau neuropathology at mole cular level, we used cDNA arrays representing 8832 genes to determine the m RNA expression profile in transgenic mice expressing the most common fronto temporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) Tau mu tation (P301L) (Nat. Genet. (2000) 402). Genes whose expression is associat ed with development of neurofibrillary tangles and neuron loss in P301L mic e 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 in tracellular transport. We propose that the expression of mutated P301L may lead to select altered expression of genes which may cause neurodegeneratio n in FTDP-17. (C) 2001 Published by Elsevier Science Ireland Ltd.