Summary:
Ageing is an inevitable natural process, which refers to the accumulation of
biological changes in an organism over time. These changes lead to physical and
functional collapse at the organism level including an increase in mortality
rate.
Malignant neoplasms were the main cause for 13% of the deaths worldwide in
2007. Therefore, the development of novel therapeutic agents and strategies to
inhibit the resistance of cancer cells to death and surveillance by the immune
system is a significant step for increasing the patients survive.
Apolipoprotein J/ clusterin is a novel therapeutic target. Its cytoprotective
role became apparent when experiments aimed to block clusterin with antisense
nucleotides (ASO) increased the survival rate of patients with prostate cancer
(clinical trials phase II).
To this end, the development, for the first time, of transgenic mice
overexpressing Apolipoprotein J/ clusterin constitutively under the regulation
of the human b-actin promoter. will give the opportunity to further investigate
and define the biological role of this protein in a mouse model. So, after
pronuclear microinjection of the transgene into mouse zygotes two transgenic
lines were obtained, which were checked for transgene transmission. The
availability of clusterin transgenic mice will enable us to study in detail and
fully understand the functional role of clusterin in the pathogenesis of
cancer, neurodegenerative diseases as well as in the regulation of longevity in
mammals.
Keywords:
Apolipoproterin J, Clusterin, Cancer, Ageing, Transgenic mice