Lack of Pwcr1/MBII-85 snoRNA is critical for neonatal lethality in Prader–Willi syndrome mouse models

@article{Ding2005LackOP,
  title={Lack of Pwcr1/MBII-85 snoRNA is critical for neonatal lethality in Prader–Willi syndrome mouse models},
  author={F Ding and Yelena Prints and Madhu S. Dhar and Dabney K. Johnson and Carmen Garnacho-Montero and Robert D. Nicholls and Uta Francke},
  journal={Mammalian Genome},
  year={2005},
  volume={16},
  pages={424-431}
}
Prader–Willi syndrome (PWS) is a neurobehavioral disorder caused by the lack of paternal expression of imprinted genes in the human chromosome region 15q11–13. Recent studies of rare human translocation patients narrowed the PWS critical genes to a 121-kb region containing PWCR1/HBII-85 and HBII-438 snoRNA genes. The existing mouse models of PWS that lack the expression of multiple genes, including Snrpn, Ube3a, and many intronic snoRNA genes, are characterized by 80%–100% neonatal lethality… 

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This is the first example in a multicellular organism of genetic deletion of a C/D box snoRNA gene resulting in a pronounced phenotype of Prader-Willi syndrome, and it is reported the deletion of PWScr.

SnoRNA Snord116 (Pwcr1/MBII-85) Deletion Causes Growth Deficiency and Hyperphagia in Mice

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A Comprehensive Review of Genetically Engineered Mouse Models for Prader-Willi Syndrome Research

Murine models of PWS unveiled the contribution of each affected gene to this multi-facetted disease, and also enabled the establishment of the minimal critical genomic region (PWScr) responsible for core symptoms, highlighting the importance of non-protein coding genes in the PWS locus.

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The study indicates that paternally expressed Snord116 is involved in the 24-h regulation of sleep physiological measures, suggesting that it is a candidate gene for the sleep disturbances that most individuals with PWS experience.

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What is currently known of the molecular targets of SNORD116 and IPW is reviewed and their roles in contributing to the Prader-Willi Syndrome phenotype are disentangled.

Genomic analysis of the chromosome 15q11-q13 Prader-Willi syndrome region and characterization of transcripts for GOLGA8E and WHCD1L1 from the proximal breakpoint region

An updated version of a sequence-based physical map for a complex chromosomal region is presented, and the possibility of polymorphism in the genomic orientation of the BP1 to BP2 region is raised.

A paternal deletion of MKRN3, MAGEL2 and NDN does not result in Prader–Willi syndrome

It is concluded that a deficiency of MKRN3, MAGEL2 and NDN is not sufficient to cause Prader–Willi syndrome, and two patients with PWS who have an atypical deletion on the paternal chromosome that does not include MKRN 3, MAGel2 andNDN are reported.

A human imprinting centre demonstrates conserved acquisition but diverged maintenance of imprinting in a mouse model for Angelman syndrome imprinting defects.

Paternal inheritance of the human PWS-IC demonstrates for the first time that a positive regulatory element in the P WS-IC has diverged, and creates the first reported mouse model for AS imprinting defects.

Analysis of candidate imprinted genes in PWS subjects with atypical genetics: a possible inactivating mutation in the SNURF/SNRPN minimal promoter

Nine probands with a firm clinical diagnosis of PWS but who had neither a typical deletion in the PWS region nor UPD(15)mat were investigated for inactivating mutations, indicating that PWS may result from a stochastic partial inactivation of important genes.
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