Deletion of PREPl causes growth impairment and hypotonia in mice.

Genetic 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)....

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Autores principales:	Anna Mari Lone, Mathias Leidl, Amanda K McFedries, James W Horner, John Creemers, Alan Saghatelian
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a4ca87502af746049f7ca21b6fbe9a60
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spelling	oai:doaj.org-article:a4ca87502af746049f7ca21b6fbe9a602021-11-18T08:30:33ZDeletion of PREPl causes growth impairment and hypotonia in mice.1932-620310.1371/journal.pone.0089160https://doaj.org/article/a4ca87502af746049f7ca21b6fbe9a602014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586561/?tool=EBIhttps://doaj.org/toc/1932-6203Genetic 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.Anna Mari LoneMathias LeidlAmanda K McFedriesJames W HornerJohn CreemersAlan SaghatelianPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89160 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Mari Lone Mathias Leidl Amanda K McFedries James W Horner John Creemers Alan Saghatelian Deletion of PREPl causes growth impairment and hypotonia in mice.
description	Genetic 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.
format	article
author	Anna Mari Lone Mathias Leidl Amanda K McFedries James W Horner John Creemers Alan Saghatelian
author_facet	Anna Mari Lone Mathias Leidl Amanda K McFedries James W Horner John Creemers Alan Saghatelian
author_sort	Anna Mari Lone
title	Deletion of PREPl causes growth impairment and hypotonia in mice.
title_short	Deletion of PREPl causes growth impairment and hypotonia in mice.
title_full	Deletion of PREPl causes growth impairment and hypotonia in mice.
title_fullStr	Deletion of PREPl causes growth impairment and hypotonia in mice.
title_full_unstemmed	Deletion of PREPl causes growth impairment and hypotonia in mice.
title_sort	deletion of prepl causes growth impairment and hypotonia in mice.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/a4ca87502af746049f7ca21b6fbe9a60
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Deletion of PREPl causes growth impairment and hypotonia in mice.

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