Brain distribution of genes related to changes in locomotor activity.

The relationship between genes and behavior, and particularly the hyperactive behavior, is clearly not linear nor monotonic. To address this problem, a database of the locomotor behavior obtained from thousands of mutant mice has been previously retrieved from the literature. Data showed that the percent of genes in the genome related to locomotor hyperactivity is probably more than 1.56%. These genes do not belong to a single neurotransmitter system or biochemical pathway. Indeed, they are probably required for the correct development of a specific neuronal network necessary to decrease locomotor activity. The present paper analyzes the brain expression pattern of the genes whose deletion is accompanied by changes in locomotor behavior. Using literature data concerning knockout mice, 46 genes whose deletion was accompanied by increased locomotor behavior, 24 genes related to decreased locomotor behavior and 23 genes not involved in locomotor behavior (but important for other brain functions) have been identified. These three groups of genes belonged to overlapping neurotransmitter systems or cellular functions. Therefore, we postulated that a better predictor of the locomotor behavior resulting from gene deletion might be the brain expression pattern. To this aim we correlated the brain expression of the genes and the locomotor activity resulting from the deletion of the same genes, using two databases (Allen Brain Atlas and SymAtlas). The results showed that the deletion of genes with higher expression level in the brain had higher probability to be accompanied by increased behavioral activity. Moreover the genes that were accompanied by locomotor hyperactivity when deleted, were more expressed in the cerebral cortex, amygdala and hippocampus compared to the genes unrelated to locomotor activity. Therefore, the prediction of the behavioral effect of a gene should take into consideration its brain distribution. Moreover, data confirmed that genes highly expressed in the brain are more likely to induce hyperactivity when deleted. Finally, it is suggested that gene mutations linked to specific behavioral abnormalities (e.g. inattention) might probably be associated to hyperactivity if the same gene has elevated brain expression.