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

Cyclin O (encoded by ) is a member of the cyclin family with regulatory functions in ciliogenesis and apoptosis. Homozygous mutations have been identified in human patients with Reduced Generation of Multiple Motile Cilia (RGMC) and conditional inactivation of 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 , we have generated a new mouse model characterized by the constitutive loss of in all tissues and followed a cohort during ageing. mice were growth impaired and developed hydrocephalus with high penetrance. In addition, some mice also developed hydrocephalus and affected and mice exhibited additional CNS defects including cortical thinning and hippocampal abnormalities. In addition to the CNS defects, both male and female mice were infertile and female mice exhibited few motile cilia in the oviduct. Our results further establish as an important gene for normal development and suggest that heterozygous CCNO mutations could underlie hydrocephalus or diminished fertility in some human patients.