deletion of the mbii-85 snorna gene cluster in mice results in postnatal growth retardation删除mbii - 85 snorna基因簇在老鼠身上导致产后生长迟缓.pdfVIP

Deletion of the MBII-85 snoRNA Gene Cluster in Mice Results in Postnatal Growth Retardation ¤ Boris V. Skryabin, Leonid V. Gubar, Birte Seeger, Jana Pfeiffer, Sergej Handel, Thomas Robeck, Elena Karpova , * ¨ Timofey S. Rozhdestvensky, Jurgen Brosius ¨ ¨ Institute of Experimental Pathology (ZMBE), University of Munster, Munster, Germany Prader-Willi syndrome (PWS [MIM 176270]) is a neurogenetic disorder characterized by decreased fetal activity, muscular hypotonia, failure to thrive, short stature, obesity, mental retardation, and hypogonadotropic hypogonad- ism. It is caused by the loss of function of one or more imprinted, paternally expressed genes on the proximal long arm of chromosome 15. Several potential PWS mouse models involving the orthologous region on chromosome 7C exist. Based on the analysis of deletions in the mouse and gene expression in PWS patients with chromosomal translocations, a critical region (PWScr) for neonatal lethality, failure to thrive, and growth retardation was narrowed to the locus containing a cluster of neuronally expressed MBII-85 small nucleolar RNA (snoRNA) genes. Here, we report the deletion of PWScr. Mice carrying the maternally inherited allele (PWScrm/pþ) are indistinguishable from wild-type mþ/p littermates. All those with the paternally inherited allele (PWScr ) consistently display postnatal growth retardation, with about 15% postnatal lethality in C57BL/6,