Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice
Prader-Willi syndrome (PWS) is a neurogenetic disorder caused by loss of paternally expressed genes on chromosome 15q11-q13. The PWS-critical region (PWScr) contains an array of non-protein coding IPW-A exons hosting intronic SNORD116 snoRNA genes. Deletion of PWScr is associated with PWS in humans...
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| Format: | Online |
| Language: | English |
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Nature Publishing Group
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742849/ |
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pubmed-47428492016-02-09 Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice Rozhdestvensky, Timofey S. Robeck, Thomas Galiveti, Chenna R. Raabe, Carsten A. Seeger, Birte Wolters, Anna Gubar, Leonid V. Brosius, Jürgen Skryabin, Boris V. Article Prader-Willi syndrome (PWS) is a neurogenetic disorder caused by loss of paternally expressed genes on chromosome 15q11-q13. The PWS-critical region (PWScr) contains an array of non-protein coding IPW-A exons hosting intronic SNORD116 snoRNA genes. Deletion of PWScr is associated with PWS in humans and growth retardation in mice exhibiting ~15% postnatal lethality in C57BL/6 background. Here we analysed a knock-in mouse containing a 5′HPRT-LoxP-NeoR cassette (5′LoxP) inserted upstream of the PWScr. When the insertion was inherited maternally in a paternal PWScr-deletion mouse model (PWScrp−/m5′LoxP), we observed compensation of growth retardation and postnatal lethality. Genomic methylation pattern and expression of protein-coding genes remained unaltered at the PWS-locus of PWScrp−/m5′LoxP mice. Interestingly, ubiquitous Snord116 and IPW-A exon transcription from the originally silent maternal chromosome was detected. In situ hybridization indicated that PWScrp−/m5′LoxP mice expressed Snord116 in brain areas similar to wild type animals. Our results suggest that the lack of PWScr RNA expression in certain brain areas could be a primary cause of the growth retardation phenotype in mice. We propose that activation of disease-associated genes on imprinted regions could lead to general therapeutic strategies in associated diseases. Nature Publishing Group 2016-02-05 /pmc/articles/PMC4742849/ /pubmed/26848093 http://dx.doi.org/10.1038/srep20398 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Rozhdestvensky, Timofey S. Robeck, Thomas Galiveti, Chenna R. Raabe, Carsten A. Seeger, Birte Wolters, Anna Gubar, Leonid V. Brosius, Jürgen Skryabin, Boris V. |
| spellingShingle |
Rozhdestvensky, Timofey S. Robeck, Thomas Galiveti, Chenna R. Raabe, Carsten A. Seeger, Birte Wolters, Anna Gubar, Leonid V. Brosius, Jürgen Skryabin, Boris V. Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice |
| author_facet |
Rozhdestvensky, Timofey S. Robeck, Thomas Galiveti, Chenna R. Raabe, Carsten A. Seeger, Birte Wolters, Anna Gubar, Leonid V. Brosius, Jürgen Skryabin, Boris V. |
| author_sort |
Rozhdestvensky, Timofey S. |
| title |
Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice |
| title_short |
Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice |
| title_full |
Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice |
| title_fullStr |
Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice |
| title_full_unstemmed |
Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice |
| title_sort |
maternal transcription of non-protein coding rnas from the pws-critical region rescues growth retardation in mice |
| description |
Prader-Willi syndrome (PWS) is a neurogenetic disorder caused by loss of paternally expressed genes on chromosome 15q11-q13. The PWS-critical region (PWScr) contains an array of non-protein coding IPW-A exons hosting intronic SNORD116 snoRNA genes. Deletion of PWScr is associated with PWS in humans and growth retardation in mice exhibiting ~15% postnatal lethality in C57BL/6 background. Here we analysed a knock-in mouse containing a 5′HPRT-LoxP-NeoR cassette (5′LoxP) inserted upstream of the PWScr. When the insertion was inherited maternally in a paternal PWScr-deletion mouse model (PWScrp−/m5′LoxP), we observed compensation of growth retardation and postnatal lethality. Genomic methylation pattern and expression of protein-coding genes remained unaltered at the PWS-locus of PWScrp−/m5′LoxP mice. Interestingly, ubiquitous Snord116 and IPW-A exon transcription from the originally silent maternal chromosome was detected. In situ hybridization indicated that PWScrp−/m5′LoxP mice expressed Snord116 in brain areas similar to wild type animals. Our results suggest that the lack of PWScr RNA expression in certain brain areas could be a primary cause of the growth retardation phenotype in mice. We propose that activation of disease-associated genes on imprinted regions could lead to general therapeutic strategies in associated diseases. |
| publisher |
Nature Publishing Group |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742849/ |
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1613534416396615680 |