Genes and a 3-Mb deletion mapping to human chromosome 22q11.2 have been implicated in 22q11.2 deletion syndrome (22q11.2DS) and schizophrenia. The Df1 heterozygous (Df1/+) mice, a model for 22q11.2DS, display specific deficits in hippocampus-dependent learning and memory and impaired sensorimotor gating, abnormalities observed in patients with schizophrenia and 22q11.2DS. In light of the analogous behavioral abnormalities observed between the Df1/+ mice and 22q11.2DS and schizophrenia respectively, particularly in association with the 22q11.2 deletion, the Df1/+ mice are suitable for investigating the molecular changes that may underlie the cognitive deficits and behavioral abnormalities arising as a result of this deletion. Hence we applied microarray technology to identify such molecular changes in the hippocampus at the transcript level. Twelve genes mapping to the deleted region were reliably identified as expressed in the hippocampus by microarray analysis. 159 other differentially expressed genes/ESTs were also identified. Thus far differential expression of fifteen of these genes involved in signal transduction, synaptic plasticity, neuronal differentiation, microtubule assembly and ubiquitin pathway relevant to hippocampus mediated function have been confirmed by real-time PCR. Of particular interest is the decreased expression (32%) of calmodulin 1, encoding a calcium-dependent protein involved in the calmodulin-calcineurin regulated pathway implicated in learning and memory.