Constitutive Cyclin O deficiency results in penetrant hydrocephalus, impaired growth and infertility

Núñez Ollé, Marc, 1984-; Jung, Carole; Terré, Berta; Balsiger, Norman A.; Plata, Cristina; Roset i Huguet, Ramon; Pardo Pastor, Carlos; Garrido, Marta; Rojas, Santiago; Alameda Quitllet, Francisco; Lloreta, Josep, 1958-; Martín Caballero, Juan; Flores, Juana M.; Stracker, Travis; Valverde, M. A. (Miguel Ángel), 1963-; Muñoz López, Francisco José, 1964-; Gil Gómez, Gabriel

Constitutive Cyclin O deficiency results in penetrant hydrocephalus, impaired growth and infertility

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dc.contributor.author Núñez Ollé, Marc, 1984-ca
dc.contributor.author Jung, Caroleca
dc.contributor.author Terré, Bertaca
dc.contributor.author Balsiger, Norman A.ca
dc.contributor.author Plata, Cristinaca
dc.contributor.author Roset i Huguet, Ramonca
dc.contributor.author Pardo Pastor, Carlosca
dc.contributor.author Garrido, Martaca
dc.contributor.author Rojas, Santiagoca
dc.contributor.author Alameda Quitllet, Franciscoca
dc.contributor.author Lloreta, Josep, 1958-ca
dc.contributor.author Martín Caballero, Juanca
dc.contributor.author Flores, Juana M.ca
dc.contributor.author Stracker, Travisca
dc.contributor.author Valverde, M. A. (Miguel Ángel), 1963-ca
dc.contributor.author Muñoz López, Francisco José, 1964-ca
dc.contributor.author Gil Gómez, Gabrielca
dc.date.accessioned 2018-03-21T08:06:07Z
dc.date.available 2018-03-21T08:06:07Z
dc.date.issued 2017
dc.description.abstract Cyclin O (encoded by CCNO) is a member of the cyclin family with regulatory functions in ciliogenesis and apoptosis. Homozygous CCNO mutations have been identified in human patients with Reduced Generation of Multiple Motile Cilia (RGMC) and conditional inactivation of Ccno in the mouse recapitulates some of the pathologies associated with the human disease. These include defects in the development of motile cilia and hydrocephalus. To further investigate the functions of Ccno in vivo, we have generated a new mouse model characterized by the constitutive loss of Ccno in all tissues and followed a cohort during ageing. Ccno-/- mice were growth impaired and developed hydrocephalus with high penetrance. In addition, some Ccno+/- mice also developed hydrocephalus and affected Ccno-/- and Ccno+/- mice exhibited additional CNS defects including cortical thinning and hippocampal abnormalities. In addition to the CNS defects, both male and female Ccno-/- mice were infertile and female mice exhibited few motile cilia in the oviduct. Our results further establish CCNO as an important gene for normal development and suggest that heterozygous CCNO mutations could underlie hydrocephalus or diminished fertility in some human patients.
dc.description.sponsorship The ES cells used for this research project were generated by the trans-NIH Knock-Out Mouse Project (KOMP) and obtained from the KOMP Repository (www.komp.org). NIH grants to Velocigene at Regeneron Inc (U01HG004085) and the CSD Consortium (U01HG004080) funded the generation of gene-targeted ES cells for 8500 genes in the KOMP Program and archived and distributed by the KOMP Repository at UC Davis and CHORI (U42RR024244). G.-G. is supported by ISCIII-grant PI13/00864, FEDER Funds and by Fundació La Marató de TV3, grant 100610. MAV is supported by the Ministerio de Economía y Competitividad (SAF2015-69762R) and FEDER Funds. T.H.S. was supported by the Ministerio de Economía y Competitividad (MINECO) (BFU2015-68354, Ayudas para incentivar la incorporación estable de doctores (IED) 2015) and institutional funding from MINECO through the Centres of Excellence Severo Ochoa award and the CERCA Programme of the Catalan Government. F.J.M. was supported by the Plan Estatal de I+D+I 2013-2016 and ISCIII-grant PI13/00408 and FEDER Funds and B.T. was supported by an FPI fellowship (MINECO).
dc.format.mimetype application/pdf
dc.identifier.citation Núñez-Ollé M, Jung C, Terré B, Balsiger NA, Plata C, Roset R et al. Constitutive Cyclin O deficiency results in penetrant hydrocephalus, impaired growth and infertility. Oncotarget. 2017 Oct 12;8(59):99261-73. DOI: 10.18632/oncotarget.21818
dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.21818
dc.identifier.issn 1949-2553
dc.identifier.uri http://hdl.handle.net/10230/34220
dc.language.iso eng
dc.publisher Impact Journalsca
dc.relation.ispartof Oncotarget. 2017 Oct 12;8(59):99261-73
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-69762-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68354-P
dc.rights © Núnez-Ollé et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0) (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/3.0/
dc.subject.keyword Cyclin O
dc.subject.keyword Gerotarget
dc.subject.keyword Ciliogenesis
dc.subject.keyword Hydrocephalus
dc.subject.keyword Neurogenesis
dc.title Constitutive Cyclin O deficiency results in penetrant hydrocephalus, impaired growth and infertilityca
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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