Protecting Pax6 3’ UTR from MicroRNA-7 Partially Restores PAX6 in Islets from an Aniridia Mouse Model

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dc.contributor.authorYongblah, Kevin
dc.contributor.authorAlford, Spencer C.
dc.contributor.authorRyan, Bridget C.
dc.contributor.authorChow, Robert L.
dc.contributor.authorHoward, Perry L.
dc.date.accessioned2018-11-02T07:59:54Z
dc.date.available2018-11-02T07:59:54Z
dc.date.copyright2018en_US
dc.date.issued2018
dc.description.abstractAniridia is a rare congenital syndrome that is associated with reduced visual acuity and progressive loss of vision. Aniridia patients may also develop systemic health issues associated with defects in the pancreas, digestive, and central nervous systems. The spectrum of symptoms associated with aniridia is due to haploinsufficiency of the paired box 6 gene (PAX6) and its role in the development and maintenance of the affected tissues. Here, we isolated pancreatic islets from mice heterozygous for Pax6 to test whether a Pax6-specific miRNA suppression (target protector) strategy can restore PAX6 protein levels. We show that miR-7 and miR-375 target specific sites within the Pax6 3′ UTR in a mouse pancreatic β-insulinoma cell line. Tough decoys (Tuds) against miR-7 and miR-375 increase expression of a mouse Pax6 3′ UTR luciferase reporter and increase PAX6 protein levels in these cells. Finally, we demonstrate that the shielding of the miR-7 binding site with a target protector restores PAX6 protein levels in the Pax6 heterozygous islets. The data presented here represent a proof of concept for RNA-based therapy for the progressive defects associated with aniridia and suggest the target protector approach may be a useful therapeutic strategy for other haploinsufficiency diseases.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThe authors would like to thank the late Sharon Stewart and Wendy and Dirk Yzenbrandt for their support of aniridia research and Tracy Sutcliffe in Animal Care Services for assistance with the perfusions for islet isolation. This work was supported by funds from the Sharon Stewart Trust to P.L.H. and R.L.C. and a National Science Engineering Research Council Discovery grant (RGPIN 293181-2010 to P.L.H.).en_US
dc.identifier.citationYongblah, K., Alford, S.C., Ryan, B.C., Chow, R.L. & Howard, P.L. (2018). Protecting Pax6 3’ UTR from MicroRNA-7 Partially Restores PAX6 in Islets from an Aniridia Mouse Model. Molecular Therapy: Nucleic Acids, 13, 144-153. https://doi.org/10.1016/j.omtn.2018.08.018en_US
dc.identifier.urihttps://doi.org/10.1016/j.omtn.2018.08.018
dc.identifier.urihttp://hdl.handle.net/1828/10226
dc.language.isoenen_US
dc.publisherMolecular Therapy: Nucleic Acidsen_US
dc.subjectaniridia
dc.subjectPax6
dc.subjectmicroRNA
dc.subjecttarget protector
dc.subjectislets
dc.subject.departmentDepartment of Biology
dc.subject.departmentDepartment of Biochemistry and Microbiology
dc.titleProtecting Pax6 3’ UTR from MicroRNA-7 Partially Restores PAX6 in Islets from an Aniridia Mouse Modelen_US
dc.typeArticleen_US

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