Breeding of APP/PS1 and 3xTg AD mice
The two main distinguishing pathological hallmarks of Alzheimer’s disease (AD) are formation of extracellular plaques and intracellular neurofibrillary tangles (NFTs), leading to neuronal loss. The animal models we apply to breed make it possible to investigate behavioral changes resulting from this, but, importantly, also the cellular and molecular basis of neurodegeneration. Many behavioral tests have been used to evaluate cognitive function in these animals such that we have a substantial amount of knowledge to lean on going forward. Although the clinical symptoms of AD are typically only diagnosed once subjects have become seriously ill, the degenerative process starts many years earlier. The use of these animal models allows us to investigate the early stages of pre-clinical AD at a time point before the disease is diagnosable in the human condition.
This application is for breeding of 3xTg AD mice (mus musculus, n=700) and APP/PS1 AD mice (mus musculus, n= 440). Breeding will take place at the transgenic breeding facility AKM/CoMed (facility 102) for both APP/PS1 and 3xTg, with the relevant research going to be conducted at AKM for 3xTg mice and at the Kavli Institute for Systems Neuroscience (KIN) for APP/PS1 mice. The 3xTg mice will be obtained from Jackson laboratory, while the breeding pairs of APP/PS1 mice were donated by fellow researchers.
For the APP/PS1 model the genotype leads to development of amyloid pathology beginning at around 6 weeks. For the 3xTg AD mice, similar amyloid pathology develops and additional weak tau pathology develops from around 12 months. The well-being and health of the animals used in these experiments will be continuously monitored. They may experience some minor pain or minor confusion due to the pathology, although this is rare and most individuals do not show any signs of distress. All animals will be humanely euthanized if they show any signs of serious pain of distress. For the APP/PS1 model we have developed a method to take out neurons following human euthanasia, that allows us to keep the neurons alive and study these for more than two months in a culture. This reduced the number of animals needed since we can conduct multiple experiments on a single culture. For the 3xTG model, in non-stressful behavioral tasks we reuse animals in order to minimize the number needed. All our animals will be housed in social groups in cages containing nesting materials and shelters, toys and exercise wheels, where they are given daily check-ups by highly skilled technicians, and are also monitored by our full-time veterinary.
This application is for breeding of 3xTg AD mice (mus musculus, n=700) and APP/PS1 AD mice (mus musculus, n= 440). Breeding will take place at the transgenic breeding facility AKM/CoMed (facility 102) for both APP/PS1 and 3xTg, with the relevant research going to be conducted at AKM for 3xTg mice and at the Kavli Institute for Systems Neuroscience (KIN) for APP/PS1 mice. The 3xTg mice will be obtained from Jackson laboratory, while the breeding pairs of APP/PS1 mice were donated by fellow researchers.
For the APP/PS1 model the genotype leads to development of amyloid pathology beginning at around 6 weeks. For the 3xTg AD mice, similar amyloid pathology develops and additional weak tau pathology develops from around 12 months. The well-being and health of the animals used in these experiments will be continuously monitored. They may experience some minor pain or minor confusion due to the pathology, although this is rare and most individuals do not show any signs of distress. All animals will be humanely euthanized if they show any signs of serious pain of distress. For the APP/PS1 model we have developed a method to take out neurons following human euthanasia, that allows us to keep the neurons alive and study these for more than two months in a culture. This reduced the number of animals needed since we can conduct multiple experiments on a single culture. For the 3xTG model, in non-stressful behavioral tasks we reuse animals in order to minimize the number needed. All our animals will be housed in social groups in cages containing nesting materials and shelters, toys and exercise wheels, where they are given daily check-ups by highly skilled technicians, and are also monitored by our full-time veterinary.