The M16 mouse: an outbred animal model of early onset polygenic obesity and diabesity.
OBJECTIVE
To characterize the phenotypic consequences of long-term selective breeding for rapid weight gain, with an emphasis on obesity and obesity-induced diabetes (diabesity).


METHODS
M16 is the result of long-term selection for 3- to 6-week weight gain from an ICR base population. Experiment 1 characterized males from both lines for body weights (3, 6, and 8 weeks), feed (4 to 8 weeks) and H(2)O (6 to 8 weeks) consumption, and heat loss, body composition, and levels of several plasma proteins at 8 weeks of age. Experiment 2 characterized differences between lines for both sexes at three ages (6, 8, and 16 weeks) and fed two diets (high and normal fat). Body weight, composition, blood glucose, and plasma insulin and leptin levels were evaluated after an 8-hour fast.


RESULTS
At all ages measured, M16 mice were heavier, fatter, hyperphagic, hyperinsulinemic, and hyperleptinemic relative to ICR. M16 males and females were hyperglycemic relative to ICR, with 56% and 22% higher fasted blood glucose levels at 8 weeks of age.


CONCLUSIONS
M16 mice represent an outbred animal model to facilitate gene discovery and pathway regulation controlling early onset polygenic obesity and type 2 diabetic phenotypes. Phenotypes prevalent in the M16 model, with obesity and diabesity exhibited at a young age, closely mirror current trends in human populations.
Department of Animal Science, University of Nebraska, Lincoln, NE 68583-0908, USA.
Mark F
MF
Allan
Eugene J
EJ
Eisen
Daniel
D
Pomp
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D001833:Body Temperature Regulation; D001835:Body Weight; D001947:Breeding; D048909:Diabetes Complications / Q000235:genetics*; D004195:Disease Models, Animal; D004326:Drinking; D004435:Eating; D005260:Female; D006963:Hyperphagia / Q000235:genetics; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009765:Obesity / Q000150:complications / Q000235:genetics*; D012641:Selection, Genetic
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin