During the course of a mouse N-ethyl-N-nitrosourea (ENU) forward mutagenesis screen designed to identify enhancers of dopaminergic neurotransmission using a sensitized genetic background, we mapped a dominant mutation that increased locomotor activity in a quantitative fashion [23]. This mutation appeared to act independently of the sensitized genetic background [heterozygosity for a null mutation in the dopamine transporter [23]]. The full details of the screen, including the genomewide mapping of this locus, have been described elsewhere in [23]. Briefly, we induced mutations onto the DBA/2J (D2) strain using ENU (*) and crossed these mutagenized animals to C57BL/6J (B6) mice to create B6D2* F1 animals that were screened for increased locomotor activity when placed into a novel environment. One of these hyperactive B6D2* animals, male 28C4, was backcrossed repeatedly to B6 females yielding a population for Quantitative Trait Locus (QTL) analysis. This analysis suggested that a dominant mutation on the D2 strain on distal mouse chromosome 12 was responsible for increased locomotor response to novelty (Figure 1A). As part of the phenotypic screening, B6D2*×B6 animals were weighed between the ages of 8
