On association of the lethal yellow (A) mutation in the agouti gene with the alterations in mouse brain and behavior.

Lethal yellow (A) mutation causes obesity and type-2 diabetes in mice. Here we studied the effect of the A mutation on the brain and behavior. The experiments were carried out on adult (11-12 weeks old) males of A/a mice and their wild-type littermates (a/a). Mice of A/a and a/a genotypes did not differ in their home cage activity, sleep, food and water consumption, learning ability in the Morris water maze, anxiety in the open field and elevated plus-maze, as well as in the level of monoamines, metabolites and some genes expression in the brain. At the same time, the fat mass, depressive-like immobility in the forced swim and tail suspension tests were significantly increased in A/a mice compared with a/a ones. Magnetic resonance imaging revealed a significant reduction of cortex volume in A/a mice. The level of mRNA of Ptpn5 gene encoding striatal enriched tyrosine phosphatase in the frontal cortex of A/a mice was significantly elevated compared with their wild-type littermates. This is the first report on the alterations in the brain and behavior in the A/a mouse line. It is tempting to speculate that this mouse line can serve as a new and useful preclinical model to study neurobehavioral complications associated with obesity and type-2 diabetes.