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Home > Research > Technology Transfer > Examples of Recent Technology Transfer Initiatives > Transgenic mice expressing human P301S tau protein (continued success since 2002)

Transgenic mice expressing human P301S tau protein (continued success since 2002)

The build-up of Tau protein within neurones (Tau tangles) constitutes a defining characteristic of a number of neurodegenerative diseases, including Alzheimer’s disease, frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17).

Discovery of mutations in both coding and non-coding regions of the Tau gene has firmly established that dysfunction of tau protein can cause neurodegeneration and dementia. The age of onset of disease and the magnitude of the functional effects produced varies, depending on the Tau mutation. Mutation P301S in exon 10 of the Tau gene causes an early onset of clinical signs and has strong functional effects, leading to a reduced ability to promote microtubule assembly and an increase in aggregation.

Dr Goedert and his team generated and characterised a line of transgenic mice that constitutively express human tau with the P301S mutation (The Journal of Neuroscience, 2002, 22(21):9340). At five to six months of age, homozygous animals develop motor symptoms characterised by severe lower limb paralysis. The transgenic mouse line exhibits the essential features of a human tauopathy, including the formation of abundant filaments made of hyper-phosphorylated tau protein and nerve cell degeneration.

This mouse line expressing human mutant tau is of great value for elucidating the molecular mechanisms by which mutant tau protein causes the dysfunction and death of nerve cells. This may in turn lead to the design of new therapeutic strategies aimed at preventing tau dysfunction. Since characterisation of this mouse line was first published in 2002, the pharmaceutical industry has shown strong interest in utilising this unpatented research tool to enable in-house research and development efforts, such as testing new potential therapeutic entities for prevention, delay or amelioration of neurodegenerative disorders.

A number of big pharma and smaller biotech companies (Esai, Eli Lilly, Voyager Therapeutics, Roche, Pharma Eight Co, reMYND, Crucell Biologics, MedImmune) have acquired the mice under non-exclusive licenses, negotiated by LifeArc for the purposes of in vivo efficacy testing of proprietary compounds and biological agents, generating significant income over the years for the MRC in the form of upfront fees and annual licence fees.

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