Establisment of a novel model for aortic aneuryms in mice
Aortic aneurysm or dilatation of the main artery, is a severe condition with potentially fatal complications. To better understand the fundamental mechanisms of this disease, we will try to establish a new method for inducing aortic aneurysms in mice.
First, we will inject mice with recombinant adeno-associated viral vectors (AAV), which encode a gain of function mutation to generate a hypercholestrolemia prone mouse. This will render the mice hypercholesterolemic upon feeding a Western style diet (high fat/high cholesterol). After 3 weeks on Western diet, we will implant miniosmotic pumps with Angiotensin II (ATII), to secure steady levels of ATII, of 900 ng/kg/min. The mice will receive ATII for 4 weeks.
The purpose of the experiment/project:
To better understand the fundamental mechanisms of this disease, we will try to establish a new method for inducing aortic aneurysms in mice.
The expected adverse effects on the animals:
The animals will undergo minor procedures, and be monitored closely regarding pain/discomfort. Their genotype will not cause adverse effects during the timespan of the study. Adverse effects during the study will thereby be moderate.
The expected scientific benefits or benefits for society:
Aortic aneurysm, or dilatation of the main artery, is a severe disease with potentially fatal complications such as acute aortic regurgitation, dissection (intima tear with blood to flow between the aortic wall layers) and aortic rupture.
Without repair, the naturalhistory of aortic aneuryms is one of slow expansion, with a progressive increase in the risk of complications. Aortic aneurysms occurs most often in men aged 60+ years.
Risk factors are: Connective tissue disorders, other genetic disorders, atherosclerosis. It is important to better understand the fundamental mechanisms of this disease.
The number of animals and species:
20 mice
3Rs:
Replacement: Development of aortic aneurysms is a complex process, where many different factors such as atherosclerosis,changes in aortic wall structure and hypertension interplay. It would not be possible to replicate this outside a living organism.
Reduction: The method it self will, if successfull, contribute to reduce the amount of animals needed in further studies. Using viral vectors to induce disease will reduce the need of extensive breeding programs to get the desired genotype, and thereby reduce the amount of animals used.
Refinement: We will follow well established methods regarding minipump surgery, anesthesia and analgesia.
Mice will be monitored closely and be taken out of study if they lose > 15 % of body weight or experience medical problems/conditions.
Mice will have environmmental enrichment and housing applicable to our animal department.
First, we will inject mice with recombinant adeno-associated viral vectors (AAV), which encode a gain of function mutation to generate a hypercholestrolemia prone mouse. This will render the mice hypercholesterolemic upon feeding a Western style diet (high fat/high cholesterol). After 3 weeks on Western diet, we will implant miniosmotic pumps with Angiotensin II (ATII), to secure steady levels of ATII, of 900 ng/kg/min. The mice will receive ATII for 4 weeks.
The purpose of the experiment/project:
To better understand the fundamental mechanisms of this disease, we will try to establish a new method for inducing aortic aneurysms in mice.
The expected adverse effects on the animals:
The animals will undergo minor procedures, and be monitored closely regarding pain/discomfort. Their genotype will not cause adverse effects during the timespan of the study. Adverse effects during the study will thereby be moderate.
The expected scientific benefits or benefits for society:
Aortic aneurysm, or dilatation of the main artery, is a severe disease with potentially fatal complications such as acute aortic regurgitation, dissection (intima tear with blood to flow between the aortic wall layers) and aortic rupture.
Without repair, the naturalhistory of aortic aneuryms is one of slow expansion, with a progressive increase in the risk of complications. Aortic aneurysms occurs most often in men aged 60+ years.
Risk factors are: Connective tissue disorders, other genetic disorders, atherosclerosis. It is important to better understand the fundamental mechanisms of this disease.
The number of animals and species:
20 mice
3Rs:
Replacement: Development of aortic aneurysms is a complex process, where many different factors such as atherosclerosis,changes in aortic wall structure and hypertension interplay. It would not be possible to replicate this outside a living organism.
Reduction: The method it self will, if successfull, contribute to reduce the amount of animals needed in further studies. Using viral vectors to induce disease will reduce the need of extensive breeding programs to get the desired genotype, and thereby reduce the amount of animals used.
Refinement: We will follow well established methods regarding minipump surgery, anesthesia and analgesia.
Mice will be monitored closely and be taken out of study if they lose > 15 % of body weight or experience medical problems/conditions.
Mice will have environmmental enrichment and housing applicable to our animal department.