title: Prader-Willi syndrome transcripts are expressed in phenotypically significant regions of the developing mouse brain.
abstract: Prader-Willi syndrome (PWS) is a neurobehavioral disorder that is due to the loss of multiple, paternally-expressed, imprinted genes on human chromosome 15q11-q13. The candidate genes are conserved in mice and are located in an orthologous region on mouse 7C. Several mouse models in which one or more of the PWS candidate genes are silenced do not recapitulate the full PWS phenotype. We examined the expression patterns of the mouse orthologues of PWS candidate genes throughout the development of the brain regions most implicated in PWS, including the hypothalamus, pituitary, forebrain and hindbrain. Snrpn, Ipw and Ndn are widely expressed at high levels throughout the mouse brain, whereas Magel2, Mkrn3 and the snoRNA MBII-85 are preferentially expressed in specific brain regions. Magel2 is most specifically expressed in developing hypothalamus, the region of the brain implicated in PWS hyperphagia and obesity. Although Snrpn, Ipw and MBII-85 are putatively transcribed from the same promoter, the transcripts are differentially detected in neural tissues. The analysis of expression patterns of murine orthologues of human disease genes is valuable for identifying sites of gene expression that correlate with disease phenotype.
authors.affiliation: Department of Medical Genetics, 8-42 Medical Sciences Building, University of Alberta, Edmonton, Alta., Canada T6G 2H7.
authors.forename: Syann
authors.initials: S
authors.lastname: Lee
authors.forename: Christine L
authors.initials: CL
authors.lastname: Walker
authors.forename: Rachel
authors.initials: R
authors.lastname: Wevrick
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm; D001483:Base Sequence; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D017124:Conserved Sequence; D020869:Gene Expression Profiling; D018392:Genomic Imprinting; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000235:genetics*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins
chemical_list: D000951:Antigens, Neoplasm; D011506:Proteins; D012261:Ribonucleoproteins; D044767:Ubiquitin-Protein Ligases; C510822:MAGEL2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins; C403091:Magel2 protein, mouse; C119432:Mkrn3 protein, mouse