THE MOUSE NECDIN GENE IS EXPRESSED FROM THE PATERNAL ALLELE ONLY AND LIES IN THE 7C REGION OF THE MOUSE-CHROMOSOME-7, A REGION OF CONSERVEDSYNTENY TO THE HUMAN PRADER-WILLI-SYNDROME REGION

Prader-Willi syndrome (PWS) is a neurogenetic disorder resulting from the loss of paternal expression of gene(s) localized in the 15q11-q12 region. A new human gene encoding a putative protein with high homolog y to the mouse NECDIN protein has recently been characterized and mapp ed to chromosome 15q11-q12. It is expressed from the paternal allele o nly, suggesting its potential involvement in PWS. We now report the lo calization of the mouse Necdin gene in a region of conserved synteny t o the human PWS region. We demonstrate the paternal specific expressio n of Necdin in the mouse central nervous system, and show that parenta l alleles display a differential methylation profile in the coding reg ion, Finally, fluorescence in situ hybridization analysis reveals an a synchronous pattern of replication at the Necdin locus. These results clearly demonstrate imprinting of the mouse Necdin gene. Mouse models will be powerful tools in the study of human PWS phenotype and imprint ing mechanisms.