One of the most common genetic variations found in autism spectrum disorder (ASD) is 16p11.2 deletion syndrome. Patients with this deletion usually display developmental delay and intellectual disability, including some features of ASD. Moreover, Attention-Deficit/Hyperactivity Disorder (ADHD) is commonly reported in patients. Because the 16p11.2 chromosomal region in humans is highly conserved in mice, the 16p11.2 mouse model is considered a faithful model of disease. Using this mouse model, we previously showed both male and female 16p11.2 mice display hyperactive behavior compared to wild type sex-matched control mice. Because the striatum is the input structure of the basal ganglia, the key neural substrates for motor control, we are now investigating the role of medium spiny neurons (MSNs), the major type of neuron in the striatum, in hyperactivity in the 16p11.2 mouse model. MSNs can be characterized by their projections as either direct-pathway or indirect-pathway. The direct-pathway MSNs express dopamine receptor 1 and project to the SNr/GPi directly. To determine the role of direct-pathway or indirect-pathway MSNs in behavioral alterations of 16p11.2 mice, we use 16p11.2 flox mice, a conditioned mouse line of the 16p11.2-analogous region. Crossing them to a cell type-specific Cre mouse model or Cre-virus injection causes efficient deletion of the floxed region, allowing us to investigate the distinct role of direct-pathway or indirect-pathway MSNs. This study will help us understand the mechanisms of neurodevelopmental disorders and develop novel therapeutic approaches.