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Characterization of OXR1 mice, role in behavior

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Oxidation resistance (OXR) genes are conserved among all sequenced eukaryotes from yeast to humans. The human OXR1 gene product is widely distributed and localizes to the inner membrane and matrix of mitochondria. It plays an important role in oxidation resistance in mammalian cells and the expression is strongly regulated by the tumor-suppressor genes p21 and VHL. The molecular function of OXR1 and the biological significance in mammalian cells is not known. The purpose of this project is to study the role of OXR1 in behavior by using OXR1 KO mice.

We will use the open field test, elevated zero maze and T-maze, all of which will impose little strain on the mice. Mice tested in the T-maze will be food restricted. However, they will be weighed every day and if they reach 85% of their original weight, they will be excluded from the test and again get unlimited access to food and water. The behavioral tests will be performed by persons who have great experience with the tests. Further analyses (tissues/organs) will be performed after the mice have been euthanized.

We believe that this project will generate new knowledge regarding the role and molecular function of OXR1 in the brain, which will be important in the characterization of patients lacking functional OXR1.

In total, we apply for 640 mice (including OXR1 KO and WT mice).

The mouse genome can be easily modified and KO mice are therefore an important tool to study protein function both in healthy and sick animals. The mouse and human genomes have 95% similarity and studies done in mice will therefore in many cases give answers that can be transferred to humans. We have long-standing experience with mice and behavioral testing and the OXR1 KO model has already been generated and is available at KPM Rikshopitalet. Thus, the use of mice is an obvious choice for us in this project. To reduce the total number of mice, we will breed homozygous mice and use the same animals in different behavioral tests.