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Epigenetic alterations in tetraploid neurones and Alzheimer's disease

16th national competition for scientific and technical research

The genome and epigenome

Senior Researcher : José María Frade López

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Research Centre or Institution : Instituto Cajal. CSIC. Madrid.

Abstract

Objective 1: the establishment of a colony of Mapttm1(GFP)Klt/J mice in the animal facility of the Cajal Institute (months 1‑12).
During the first six months of the project a colony of Mapttm1(GFP)Klt/J mice was created in the animal facility of Cajal Institute, which now has two litters of these mice. These mice will be fundamental in the isolation of neurones, given that they were designed to express protein GFP in them.

Objective 2: the differentiating genomic analysis between diploid and tetraploid neurons (months 4‑12).
Optimisation has commenced on the procedure to separate diploid from tetraploid neurons, based on the brain tissue of adult mice (wild-type mice). The use of papain as the proteolytic agent aids the disassociation of cerebral cortex cells, which can be marked with DraQ5, a DNA marker that crosses the membrane and marks DNA in vivo. The aim is to use this method to isolate tetraploid neurons from Mapttm1(GFP)Klt/J mouse tissue that will then be used to analyse genetic expression using microarrays.

Objective 3: Analysis of the epigenetic mechanisms involved in the changes in genetic expression associated with neuronal tetraploidy (months 13‑36). This phase of the project has yet to start.

Objective 4: Analysis of the epigenetic mechanisms involved in the changes in genetic expression associated with AD (months 1‑36).
The expansion of APP/PS1 transgenic mice has commenced, which will be crossed with Mapttm1(GFP)Klt/J mice to obtain information on changes in genetic expression in the neurons of APP/PS1 mice.