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dc.contributor.authorSerra, Ines
dc.contributor.authorManusama, Olivia R
dc.contributor.authorKaiser, Fabian MP
dc.contributor.authorFloriano, Izi Izumi
dc.contributor.authorWahl, Lucas
dc.contributor.authorvan der Zalm, Christian
dc.contributor.authorIJspeert, Hanna
dc.contributor.authorvan Hagen, P Martin
dc.contributor.authorvan Beveren, Nico JM
dc.contributor.authorArend, Sandra M
dc.contributor.authorOkkenhaug, Klaus
dc.contributor.authorPel, Johan JM
dc.contributor.authorDalm, Virgil ASH
dc.contributor.authorBadura, Aleksandra
dc.date.accessioned2022-01-07T00:31:43Z
dc.date.available2022-01-07T00:31:43Z
dc.date.issued2021-12
dc.identifier.issn2666-3546
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332261
dc.description.abstractThe phosphoinositide-3-kinase (PI3K) family plays a major role in cell signaling and is predominant in leukocytes. Gain-of-function (GOF) mutations in the PIK3CD gene lead to the development of activated PI3Kδ syndrome (APDS), a rare primary immunodeficiency disorder. A subset of APDS patients also displays neurodevelopmental delay symptoms, suggesting a potential role of PIK3CD in cognitive and behavioural function. However, the extent and nature of the neurodevelopmental deficits has not been previously quantified. Here, we assessed the cognitive functions of two APDS patients, and investigated the causal role of the PIK3CD GOF mutation in neurological deficits using a murine model of this disease. We used p110δE1020K knock-in mice, harbouring the most common APDS mutation in patients. We found that APDS patients present with visuomotor deficits, exacerbated by autism spectrum disorder comorbidity, whereas p110δE1020K mice exhibited impairments in motor behaviour, learning and repetitive behaviour patterning. Our data indicate that PIK3CD GOF mutations increase the risk for neurodevelopmental deficits, supporting previous findings on the interplay between the nervous and the immune system. Further, our results validate the knock-in mouse model, and offer an objective assessment tool for patients that could be incorporated in diagnosis and in the evaluation of treatments.
dc.format.mediumElectronic-eCollection
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAPDS
dc.subjectASD
dc.subjectMouse
dc.subjectPID
dc.subjectPIK3CD
dc.subjectPrimary immunodeficiency
dc.titleActivated PI3Kδ syndrome, an immunodeficiency disorder, leads to sensorimotor deficits recapitulated in a murine model.
dc.typeArticle
dc.publisher.departmentDepartment of Pathology
dc.date.updated2022-01-06T11:24:38Z
prism.number100377
prism.publicationDate2021
prism.publicationNameBrain Behav Immun Health
prism.startingPage100377
prism.volume18
dc.identifier.doi10.17863/CAM.79706
dcterms.dateAccepted2021-10-18
rioxxterms.versionofrecord10.1016/j.bbih.2021.100377
rioxxterms.versionVoR
dc.contributor.orcidOkkenhaug, Klaus [0000-0002-9432-4051]
dc.identifier.eissn2666-3546
rioxxterms.typeJournal Article/Review
cam.depositDate2022-01-06
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International