Abstract: The invention relates to an animal model of cardiovascular disease and a method of preparation and use thereof. In particular, it relates to a genetically engineered animal model of aortic aneurysms and methods for screening drugs using the animal model. Provided is a genetically-modified, non-human mammal, wherein the modification results in a disrupted Fibulin-4 gene. Also provided is a genetically-modified animal cell containing a disrupted Fibulin-4 gene. The mammal or animal cell can be used as a model for a cardiovascular condition or disease, preferably aortic aneurysm, more preferably thoracic aortic aneurysm. Furthermore, methods for identify or validating a compound that can be used to treat or to prevent an aberrant cardiovascular condition are provided, as well as method to identify a gene involved in the response to aortic failure.

Abstract: The present invention relates to a method of treating or preventing hyperproliferative disease in a body tissue of a subject, comprising the steps of administering to a subject in need thereof a therapeutically effective amount of an agent that induces double strand breaks in the DNA of the hyperproliferative cells of said body tissue; and subjecting the hyperproliferative cells of said body tissue prior to, simultaneously with or subsequent to step a) to hyperthermia to thereby induce in said cells the degradation, inhibition and/or inactivation of BRCA2.

Abstract: The invention relates to an animal model of cardiovascular disease and a method of preparation and use thereof. In particular, it relates to a genetically engineered animal model of aortic aneurysms and methods for screening drugs using the animal model. Provided is a genetically-modified, non-human mammal, wherein the modification results in a disrupted Fibulin-4 gene. Also provided is a genetically-modified animal cell containing a disrupted Fibulin-4 gene. The mammal or animal cell can be used as a model for a cardiovascular condition or disease, preferably aortic aneurysm, more preferably thoracic aortic aneurysm. Furthermore, methods for identify or validating a compound that can be used to treat or to prevent an aberrant cardiovascular condition are provided, as well as method to identify a gene involved in the response to aortic failure.

Abstract: The current invention pertains to a method for screening and discovery of compounds capable of inhibiting, preventing, delaying or reducing genome maintenance disorders and consequences thereof, in particular ageing related symptoms and disorders. The current invention provides a method for screening and discovery of compounds that are capable of inhibiting, preventing, delaying or reducing genome maintenance disorders and consequences thereof. The invention exploits animal models that comprise deficiencies in their genome maintenance systems, such as DNA repair systems, and display premature, enhanced, accelerated or segmental ageing phenotypes. These animal models can be advantageously applied to screen compounds and thereby develop schemes of intervention to treat, delay, inhibit, prevent or cure ageing related symptoms. The current invention thus provides a new and powerful tool to screen aid/or discover therapeutically active compounds to treat ageing related symptoms and diseases.