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dc.contributor.authorLone, Anna Marien_US
dc.contributor.authorLeidl, Mathiasen_US
dc.contributor.authorMcFedries, Amanda K.en_US
dc.contributor.authorHorner, James W.en_US
dc.contributor.authorCreemers, Johnen_US
dc.contributor.authorSaghatelian, Alanen_US
dc.date.accessioned2014-04-11T14:11:57Z
dc.date.issued2014en_US
dc.identifier.citationLone, Anna Mari, Mathias Leidl, Amanda K. McFedries, James W. Horner, John Creemers, and Alan Saghatelian. 2014. “Deletion of Prepl Causes Growth Impairment and Hypotonia in Mice.” PLoS ONE 9 (2): e89160. doi:10.1371/journal.pone.0089160. http://dx.doi.org/10.1371/journal.pone.0089160.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12064428
dc.description.abstractGenetic studies of rare diseases can identify genes of unknown function that strongly impact human physiology. Prolyl endopeptidase-like (PREPL) is an uncharacterized member of the prolyl peptidase family that was discovered because of its deletion in humans with hypotonia-cystinuria syndrome (HCS). HCS is characterized by a number of physiological changes including diminished growth and neonatal hypotonia or low muscle tone. HCS patients have deletions in other genes as well, making it difficult to tease apart the specific role of PREPL. Here, we develop a PREPL null (PREPL−/−) mouse model to address the physiological role of this enzyme. Deletion of exon 11 from the Prepl gene, which encodes key catalytic amino acids, leads to a loss of PREPL protein as well as lower Prepl mRNA levels. PREPL−/− mice have a pronounced growth phenotype, being significantly shorter and lighter than their wild type (PREPL+/+) counterparts. A righting assay revealed that PREPL−/− pups took significantly longer than PREPL+/+ pups to right themselves when placed on their backs. This deficit indicates that PREPL−/− mice suffer from neonatal hypotonia. According to these results, PREPL regulates growth and neonatal hypotonia in mice, which supports the idea that PREPL causes diminished growth and neonatal hypotonia in humans with HCS. These animals provide a valuable asset in deciphering the underlying biochemical, cellular and physiological pathways that link PREPL to HCS, and this may eventually lead to new insights in the treatment of this disease.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0089160en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938459/pdf/en
dash.licenseLAAen_US
dc.subjectBiologyen
dc.subjectBiochemistryen
dc.subjectEnzymesen
dc.subjectGeneticsen
dc.subjectAnimal geneticsen
dc.subjectModel organismsen
dc.subjectAnimal modelsen
dc.subjectMouseen
dc.titleDeletion of Prepl Causes Growth Impairment and Hypotonia in Miceen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorLeidl, Mathiasen_US
dc.date.available2014-04-11T14:11:57Z
dc.identifier.doi10.1371/journal.pone.0089160*
dash.contributor.affiliatedLeidl, Mathias
dash.contributor.affiliatedMcFedries, Amanda
dash.contributor.affiliatedSaghatelian, Alan


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