Forsøksdyr: Ubiad1

Godkjenningsdato 09.06.2020

Godkjenningsperiode 09.06.2020-08.06.2024

Disturbances in energy metabolism can lead to obesity and associated metabolic disorders such as type 2 diabetes. We have identified Ubiad1 (UbiA prenyltransferase domain containing 1) to affect obesity using a genetic screening in mice. Ubiad1 might interact with vitamin k2 for its protective effect.

We will do measurements of energy metabolism in mice: performe metabolic phenotyping (Phenomaster, TSE systems); measurement of body mass composition (MRI/DEXA); and standard insulin, glucose and pyruvate tolerance tests. According to §10, the purpose is: a) Basal forskning.

Expected distress:
The whole animal proposal is rated as a “Moderate Experiment” with low expected distress for most animals. Severity classification of various procedures: 1) Blood sampling: Minimal. 2) Modified diets with altered energy composition that meets all nutritional requirements: Minimal. 3) Extra vitamin K added to the water or diet: Minimal. 4) Food withdraw for up to 16 hours: Minimal/moderate. 4) Metabolic Phenotyping: Minimal/moderate. 6) metabolic tolerance tests: Minimal/moderate. 7) Body composition measurements: Minimal.

We will perform all the described procedures on each mouse, except only one of the metabolic tolerance tests per animal (insulin, glucose or pyruvate tolerance tests). In more detail: mice will be fed a chow or high fat diet for 8 weeks, with or without vitamin K2 added to the diet or water. Blood sampling from the tail will be performed together with the metabolic tolerance tests. Body composition measurements will be performed weekly. Metabolic tolerance test will be performed after 6-7 weeks of diet intervention. The mice will be moderately food withdrawed prior to euthanasia (to normalize blood glucose parameters).

Expected benefits:
The obtained results will clarify if genetically modified mice with a non-functional Ubiad1 gene have altered metabolism. We will test Ubiad1+/+ mice against Ubiad1+/- or whole body Ubiad1-/-. This will decide if Ubiad1 is a target to combat obesity.

Number and type of animals:
The model is new and an animal welfare assessment has not been carried out. The proposal includes mice anticipated used the next 4 years. Mice of both genders will be given two different diets (with and without vitamin K2 supplementation). Genotypes used: Ubiad1+/+, Ubiad1+/- and Ubiad1-/- . In total we apply to use 1500 mice over 4 years for experiments and breeding. We will strive to use as few mice as possible.

Adherence to the 3Rs:
The laboratory mouse is a good model to study gene functions and human disease, with a physiology similar to humans and well-established methods for genetic modifications. The metabolic phenotyping will often be followed by collection of organs, tissues and cells for further analysis, a type of sampling that would be impossible with human subjects. Alternatives to these experiments, where genetically modified animals and altered diets are combined, cannot be performed in human subjects. Standardized experiments conducted by specially trained personnel will reduce experimental variation and the total number of animals needed for these experiments.