Breeding of DNA glycosylase deficient mice
Oxidative DNA damage arises as a consequence of normal metabolism but also by various environmental stimuli, and is believed to play an important role in the development of cancer and normal aging. Oxidative DNA damage is primarily repaired by the base excision repair (BER) pathway. DNA glycosylases initiate BER by recognizing and excising the damaged base. To date, six mammalian DNA glycosylases that remove a variety of oxidative base lesions have been identified.
So far, no severe phenotypes have been observed in single KO mice. The OGG/Muty DO KO has shown an increased cancer susceptibility, so we will sacrifice these at the age of 6 months, before developing cancer. We would like to use Neil1 KO, Neil2 KO, Neil3 KO, Ogg1 KO, Muty KO, OGG/Muty DO KO, Neil1/Neil2 DO KO, and C57/bl6N as a control for all KO model, to further elucidate the role of DNA glycosylases in cancer development, aging and memory formation.
To date it is not possible to model those complex diseases in vitro without the use of appropriate animal models. Since this application is for breeding only, no adverse effects are expected. All our experiments are well planned to avoid an excess use of animals. Animals, which are used for breeding, will be included in the experiments for the late time points to reduce the total amount of mice needed for the analyses.
We apply for 2080 animals over 4 years. Most of these mice will be used in other research projects, so we expect the number of mice used for breeding only to be a lot less than 2080.
So far, no severe phenotypes have been observed in single KO mice. The OGG/Muty DO KO has shown an increased cancer susceptibility, so we will sacrifice these at the age of 6 months, before developing cancer. We would like to use Neil1 KO, Neil2 KO, Neil3 KO, Ogg1 KO, Muty KO, OGG/Muty DO KO, Neil1/Neil2 DO KO, and C57/bl6N as a control for all KO model, to further elucidate the role of DNA glycosylases in cancer development, aging and memory formation.
To date it is not possible to model those complex diseases in vitro without the use of appropriate animal models. Since this application is for breeding only, no adverse effects are expected. All our experiments are well planned to avoid an excess use of animals. Animals, which are used for breeding, will be included in the experiments for the late time points to reduce the total amount of mice needed for the analyses.
We apply for 2080 animals over 4 years. Most of these mice will be used in other research projects, so we expect the number of mice used for breeding only to be a lot less than 2080.