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dc.contributor.authorMartinez, M Elenaen
dc.contributor.authorCharalambous, Marikaen
dc.contributor.authorSaferali, Aabidaen
dc.contributor.authorFiering, Stevenen
dc.contributor.authorNaumova, Anna Ken
dc.contributor.authorSt, Germain Donalden
dc.contributor.authorFerguson-Smith, Anneen
dc.contributor.authorHernandez, Arturoen
dc.date.accessioned2014-10-02T09:05:32Z
dc.date.available2014-10-02T09:05:32Z
dc.date.issued2014-09-18en
dc.identifier.citationMolecular Endocrinology 28(11):1875-86. doi: 10.1210/me.2014-1210.en
dc.identifier.issn0888-8809
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/246100
dc.description.abstractThe Dio3 gene, which encodes for the type 3 deiodinase (D3), controls thyroid hormone (TH) availability. The lack of D3 in mice results in tissue overexposure to TH, and a broad neuroendocrine phenotype. Dio3 is an imprinted gene, preferentially expressed from the paternally inherited allele in the mouse fetus. However, heterozygous mice with paternal inheritance of the inactivating Dio3 mutation exhibit an attenuated phenotype when compared to that of Dio3 null mice. To investigate this milder phenotype, allelic expression of Dio3 was evaluated in different mouse tissues. Preferential allelic expression of Dio3 from the paternal allele was observed in fetal tissues and neonatal brain regions, while biallelic Dio3 expression occurred in the developing eye, testes, cerebellum and in the postnatal brain neo-cortex, which expresses a larger Dio3 mRNA transcript. The newborn hypothalamus manifests the highest degree of Dio3 expression from the paternal allele, compared to other brain regions, and preferential allelic expression of Dio3 in the brain relaxed in late neonatal life. Methylation analysis of two regulatory regions of the Dio3 imprinted domain revealed modest but significant differences between tissues, but these did not consistently correlate with the observed patterns of Dio3 allelic expression. Deletion of the Dio3 gene and promoter did not result in significant changes in the tissue-specific patterns of Dio3 allelic expression. These results suggest the existence of unidentified epigenetic determinants of tissue-specific Dio3 imprinting. The resulting variation in Dio3 allelic expression between tissues likely explains the phenotypic variation that results from paternal Dio3 haplo-insufficiency.
dc.languageen_USen
dc.language.isoen_USen
dc.publisherEndocrine Society
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.titleGenomic Imprinting Variations in the Mouse Type 3 Deiodinase Gene Between Tissues and Brain Regionsen
dc.typeArticle
dc.description.versionThis is the final version of the article. It is available from the Endocrine Society in Molecular Endocrinology here: http://press.endocrine.org/doi/pdf/10.1210/me.2014-1210.en
prism.endingPage1886
prism.publicationDate2014en
prism.publicationNameMolecular Endocrinologyen
prism.startingPage1875
prism.volume28en
dc.rioxxterms.funderMedical Research Council
dc.rioxxterms.funderWellcome Trust
rioxxterms.versionofrecord10.1210/me.2014-1210en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2014-09-18en
dc.contributor.orcidFerguson-Smith, Anne [0000-0003-4996-9990]
dc.identifier.eissn1944-9917
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MR/J001597/1)
pubs.funder-project-idWellcome Trust (095606/Z/11/Z)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales