Constitutive Cyclin O deficiency results in penetrant hydrocephalus, impaired growth and infertility
Núnez-Ollé, Marc (Institut Hospital del Mar d'Investigacions Mèdiques)
Jung, Carole (Universitat Pompeu Fabra. Laboratori de Fisiologia Molecular)
Terré, Berta (Institute for Research in Biomedicine (IRB Barcelona))
Balsiger, Norman A. (Institut Hospital del Mar d'Investigacions Mèdiques)
Plata, Cristina (Universitat Pompeu Fabra. Laboratori de Fisiologia Molecular)
Roset, Ramon (Institut Hospital del Mar d'Investigacions Mèdiques)
Pardo-Pastor, Carlos (Universitat Pompeu Fabra. Laboratori de Fisiologia Molecular)
Garrido, Marta (Institut Hospital del Mar d'Investigacions Mèdiques)
Rojas, Santiago (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques)
Alameda, Francesc (Institut Hospital del Mar d'Investigacions Mèdiques)
Lloreta, Josep 1958- (Institut Hospital del Mar d'Investigacions Mèdiques)
Martín-Caballero, Juan (Parc de Recerca Biomèdica de Barcelona (PRBB))
Flores, Juana M. (Universidad Complutense de Madrid. Departamento de Medicina y Cirugía Animal)
Stracker, Travis H. (Institute for Research in Biomedicine (IRB Barcelona))
Valverde, Miguel A. (Universitat Pompeu Fabra. Laboratori de Fisiologia Molecular)
Muñoz, Francisco J. (Universitat Pompeu Fabra. Laboratori de Fisiologia Molecular)
Gil-Gómez, Gabriel (Institut Hospital del Mar d'Investigacions Mèdiques)
Universitat Autònoma de Barcelona

Data:	2017
Resum:	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.
Ajuts:	Instituto de Salud Carlos III PI13-00864 Instituto de Salud Carlos III PI13-00408 Ministerio de Economía y Competitividad SAF2015-69762 Ministerio de Economía y Competitividad BFU2015-68354
Nota:	Altres ajuts: 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 FEDER Funds and by Fundació La Marató de TV3, grant 100610.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cyclin O ; Ciliogenesis ; Neurogenesis ; Hydrocephalus ; Development ; Gerotarget
Publicat a:	Oncotarget, Vol. 8 (october 2017) , p. 99261-99273, ISSN 1949-2553

DOI: 10.18632/oncotarget.21818
PMID: 29245899

13 p, 5.0 MB

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