The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse

Human chromosome 15q11-q13 contains genes that are imprinted and expressedfrom only one parental allele. Prader-Willi syndrome (PWS) is due to theloss of expression of one or more paternally expressed genes on proximalhuman chromosome 15q, most often by deletion or maternal uniparentaldisomy. Several candidate genes and a putative imprinting centre have beenidentified in the deletion region. We report that the human necdin-encodinggene (NDN) is within the centromeric portion of the PWS deletion region,between the two imprinted genes ZNF127 and SNRPN. Murine necdin is anuclear protein expressed exclusively in differentiated neurons in thebrain. Necdin is postulated to govern the permanent arrest of cell growthof post-mitotic neurons during murine nervous system development. We havelocalized the mouse locus Ndn encoding necdin to chromosome 7 in a regionof conserved synteny with human chromosome 15q11-q13, by genetic mapping inan interspecific backcross panel. Furthermore, we demonstrate thatexpression of Ndn is limited to the paternal allele in RNA from newbornmouse brain. Expression of NDN is detected in many human tissues, withhighest levels of expression in brain and placenta. NDN is expressedexclusively from the paternally inherited allele in human fibroblasts. Lossof necdin gene expression may contribute to the disorder of braindevelopment in individuals with PWS.