In mice, over-expression of ITPKB protein leads to exacerbation of Alzheimer's disease. Moreover, inhibition of ITPKB in cultured mouse neurons limits the production of amyloid peptides responsible for the formation of senile plaques.
Professor Stéphane Schurmans, director of the GIGA Functional Genetics Laboratory at the University of Liège, reveals the results of his work in a study published in Brain.

Genes hold the information required for making proteins, essential elements for living cells and hence life itself. Gene sequencing enables us to understand the composition of respective proteins, but not their function. However, proteins may play a multitude of different roles within the cell, because they ensure the vast majority of cell function. Proteins may thus play a role in structuring, catalysing and regulating DNA packaging, as well as in cell mobility and even gene expression.

To study the role of genes and the proteins which they encode, scientists use different techniques. 'For example, for enzymes, we can look at the substrates to which they bind, or to the product which results from the reaction that the enzyme catalyses, but also at the speed of this reaction or even try to determine where the enzyme is expressed. All these data enable us to obtain information on the role of this protein', explains Stéphane Schurmans, Director of the GIGA Laboratory of Functional Genetics at the University of Liège. 'But the ultimate aim is to be able to study the function of genes in vivo, i.e. at the level of the complete, living animal' he continues. And this is precisely the area which Stéphane Schurmans has been studying since 1992. He has genetically modified lab mice to obtain knock-out mice strains for target genes, i.e. mice in which a particular gene is inactivated. Around fifteen knock-out mice were created in the laboratory.

From the immune system to the nervous system

In 2003, Stéphane Schurmans and his team obtained the first knock-out mouse for the ITPKB gene (inositol 1, 4, 5 triphosphate 3-kinase B). 'We then discovered that these mice presented a particular phenotype because they did not have peripheral T lymphocytes , i.e. in the lymph nodes and the spleen', continues Professor Schurmans. Additional studies showed that other cells in the immune system, such as B lymphocytes, neutrophils, myeloid cells, and mast cells were also altered in ITPKB knock-out mice. 'These results show the importance of the role of the ITPKB enzyme in the haematopoietic system and the immune system', says the researcher. Thus, the ITPKB knock-out mice logically could be useful for the study of the ITPKB enzyme function within these biological systems.