title: A targeted deletion upstream of Snrpn does not result in an imprinting defect.
abstract: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) result from the disturbance of imprinted gene expression within human chromosome 15q11-q13. Some cases of PWS and AS are caused by microdeletions near the SNRPN gene that disrupt a regulatory element termed the imprinting center (IC). The IC has two functional components; an element at the promoter of SNRPN involved in PWS (PWS-IC) and an element 35 kilobases (kb) upstream of SNRPN involved in AS (AS-IC). To further understand the function of the IC, we sought to create a mouse model for AS-IC mutations. We have generated two deletions at a location analogous to that of the human AS-IC. Neither deletion produced an imprinting defect as indicated by DNA methylation and gene expression analyses. These results indicate that no elements critical for AS-IC function in mouse reside within the 12.8-kb deleted region and suggest that the specific location of the AS-IC is not conserved between human and mouse.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida 32610-0266, USA.
authors.forename: Edwin G
authors.initials: EG
authors.lastname: Peery
authors.forename: Michael D
authors.initials: MD
authors.lastname: Elmore
authors.forename: James L
authors.initials: JL
authors.lastname: Resnick
authors.forename: Camilynn I
authors.initials: CI
authors.lastname: Brannan
authors.forename: Karen A
authors.initials: KA
authors.lastname: Johnstone
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics; D000818:Animals; D001324:Autoantigens / Q000235:genetics*; D001483:Base Sequence; D019175:DNA Methylation; D018392:Genomic Imprinting / Q000235:genetics*; D040582:Inheritance Patterns / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D012097:Repressor Proteins / Q000235:genetics; D012261:Ribonucleoproteins / Q000235:genetics; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D055517:snRNP Core Proteins
chemical_list: D001324:Autoantigens; D012097:Repressor Proteins; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; C526417:SNRPN protein, human; D055517:snRNP Core Proteins; C502429:Ube3a protein, mouse; C119432:Mkrn3 protein, mouse; D044767:Ubiquitin-Protein Ligases