Unknown

Dataset Information

0

Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice.


ABSTRACT: 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-Neo(R) cassette (5'LoxP) inserted upstream of the PWScr. When the insertion was inherited maternally in a paternal PWScr-deletion mouse model (PWScr(p-/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 PWScr(p-/m5'LoxP) mice. Interestingly, ubiquitous Snord116 and IPW-A exon transcription from the originally silent maternal chromosome was detected. In situ hybridization indicated that PWScr(p-/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.

SUBMITTER: Rozhdestvensky TS 

PROVIDER: S-EPMC4742849 | BioStudies | 2016-01-01

SECONDARY ACCESSION(S): 105830

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC5824864 | BioStudies
2007-01-01 | S-EPMC2323313 | BioStudies
| S-EPMC5815655 | BioStudies
2019-01-01 | S-EPMC6527448 | BioStudies
1000-01-01 | S-EPMC3656643 | BioStudies
2014-01-01 | S-EPMC3976333 | BioStudies
2008-01-01 | S-EPMC2248623 | BioStudies
1000-01-01 | S-EPMC4698587 | BioStudies
2018-01-01 | S-EPMC6240740 | BioStudies
2013-01-01 | S-EPMC3752217 | BioStudies