Prader-Willi Syndrome (PWS) is a neurodevelopmental disorder caused by the loss of the expression of the paternally expressed genes contained at PWS locus, located at chromosome 15 in humans. The most common molecular cause of the syndrome is a deletion of some of the genes located in this cluster, and specifically, a critical region (PWScr) has been postulated as the minimal deletion capable of giving rise to a PWS phenotype. This region contains several tandem-repeated copies of snoRNA-coding gene SNORD116 and the non-coding gene IPW. In adult mammals, new neurons are produced along the whole life due to the presence of neural stem cells (NSCs) located in two main niches: the subventricular zone (SVZ) in the walls of the lateral ventricles and the subgranular zone (SGZ) in the dentate gyrus of the hippocampus. Here, we use a mouse model of PWS lacking the paternal copy of the PWScr to determine whether gene expression is affected in the hippocampus of a mouse model of PWS lacking the paternal copy of the PWScr. We have found a widely altered transcriptome in the hippocampus of PWS mice, suggesting hippocampal impairment in our mouse model of PWS. We also analysed immunohistochemically the adult SGZ neurogenesis of PWS mice and found an altered number of doublecortin (DCX)+ cells in the dentate gyrus compared to their wildtype littermates, indicating that the neurogenic process in this niche is affected.