Forsøksdyr: NTS - Metabolic Phenotyping Core Facility


Godkjenningsdato 01.02.2018

Purpose:
Whole body energy balance is dependent upon various components of energy intake and energy expenditure that needs to be assessed simultaneously to elucidate whole-body metabolism. Disturbances in energy metabolism can lead to obesity and associated metabolic disorders such as type 2 diabetes, hypertension and cardiovascular diseases, and may be linked to certain types of cancers, cognitive dysfunction and neurodegenerative diseases. Measurement of metabolism may therefore help to understand human diseases.

Many genetically modified mice have altered metabolism. A detailed phenotypical characterization og such genetically midifed animals may help to understand the phenotype or function of a gene. For this purpose, NTS has established a new core facility for measurement of energy metabolism in mice. The core consists of a platform for metabolic phenotyping (Phenomaster, TSE systems), a treadmill for exercise studies (4-lane treadmill, TSE systems), measurement of body mass composition (MRI/DEXA), and standard insulin, glucose and pyruvate tolerance tests. The metabolic phenotyping core will perform services for the research community. 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) Fasting for up 24 hours: Minimal/moderate. 4) Metabolic Phenotyping: Minimal/moderate. 5) Exercise: no/minimal. 6) metabolic tolerance tests: Minimal/moderate. 7) Body composition measurements: Minimal.

Expected benefits:
The obtained results will clarify if various genetically modified lines have altered metabolism. This knowledge will increase our understanding of gene functions and might help to unravel new molecular mechanisms that can be targeted to treat human diseases.

Number and type of animals:
This service is quite demanding, but new in Norway. The interest from the scientific research community is difficult to anticipate. The proposal includes a reasonable amount of mice anticipated used the next 4 years. Each metabolic phenotyping experiment wiht a maximum of 20 animals will last for up to one week. Provided that the instrument is operated at 50 % capacity, the number of mice used will be 0.5 x 20 mice x 50 weeks = 500 mice/year. In total it is applied for 500 mice x 4 years = 2000 mice.

Adherence to the 3Rs:
These analyses will supplement other experiments performed by various research groups. 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.