Activated PI3Kδ syndrome, an immunodeficiency disorder, leads to sensorimotor deficits recapitulated in a murine model

Serra, Ines; Manusama, Olivia; Kaiser, Fabian; Floriano, Izi Izumi; Wahl, Lucas; Zalm, Christian van der; IJspeert, Hanna; Hagen, P. Martin van; Beveren, Nico J.M. van; Arend, Sandra M.; Okkenhaug, Klaus; Pel, J.J.M.; Dalm, Virgil A. S. H.; Badura, Aleksandra

doi:10.1101/2021.01.15.426862

Cited by 2 publications

(1 citation statement)

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“…The copyright holder for this preprint this version posted October 16, 2021. ; https://doi.org/10.1101/2021.10.16.464233 doi: bioRxiv preprint laboratories only use visual scoring of buried marbles as a proxy for burying behavior, which fails to include many of the features of actual behavior in the analysis, disregarding possible changes in burying patterns that are not visible in the end result. Rare studies make use of images or video recordings, though analysis is often still done with manual annotation of frames (Serra et al, 2021). This method is highly time-consuming and is therefore not widely adopted.…”

Section: Introductionmentioning

confidence: 99%

A novel automated approach for improving standardization of the marble burying test enables quantification of burying bouts and activity characteristics

Wahl

Punt

Arbab

et al. 2021

Preprint

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The marble burying test is a commonly used paradigm to screen phenotypes in mouse models of neurodevelopmental and psychiatric disorders. The current methodological approach relies solely on reporting the number of buried marbles at the end of the test. By measuring the proxy of the behavior (buried marbles), rather than the behavior itself (burying bouts), many important characteristics regarding the temporal aspect of this assay are lost. Here we introduce a novel, automated method to quantify mouse behavior throughout the duration of the marble burying test with the focus on the burying bouts. Using open-source software packages, we trained a supervised machine learning algorithm (the classifier) to distinguish burying behavior in freely moving mice. In order to confirm the classifier's accuracy and uncover the behavioral meaning of the marble burying test, we performed marble burying test in three mouse models: Ube3am-/p+ (Angelman Syndrome model), Shank2-/- (autism model), and Sapap3-/- (obsessive-compulsive disorder model) mice. The classifier scored burying behavior accurately and consistent with the literature in the Ube3am-/p+ mice, which showed decreased levels of burying compared to controls. Shank2-/- mice showed a similar pattern of decreased burying behavior, which was not found in Sapap3-/- mice. Tracking mouse behavior throughout the test enabled us to quantify activity characteristics, revealing hypoactivity in Ube3am-/p+ and hyperactivity in the Shank2-/- mice, indicating that mouse activity is unrelated to burying behavior. Together, we demonstrate that our classifier is an accurate method for the analysis of the marble burying test, providing more information than the currently used methods.

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Section: Introductionmentioning

confidence: 99%

A novel automated approach for improving standardization of the marble burying test enables quantification of burying bouts and activity characteristics

Wahl

Punt

Arbab

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

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Two Monogenetic Disorders, Activated PI3-Kinase-δ Syndrome 2 and Smith–Magenis Syndrome, in One Patient: Case Report and a Literature Review of Neurodevelopmental Impact in Primary Immunodeficiencies Associated With Disturbed PI3K Signaling

et al. 2021

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Activated PI3-kinase-δ syndrome 2 (APDS2) is caused by autosomal dominant mutations in the PIK3R1 gene encoding the p85α, p55α, and p50α regulatory subunits. Most diagnosed APDS2 patients carry mutations affecting either the splice donor or splice acceptor sites of exon 11 of the PIK3R1 gene responsible for an alternative splice product and a shortened protein. The clinical presentation of APDS2 patients is highly variable, ranging from mild to profound combined immunodeficiency features as massive lymphoproliferation, increased susceptibility to bacterial and viral infections, bronchiectasis, autoimmune manifestations, and occurrence of cancer. Non-immunological features such as growth retardation and neurodevelopmental delay have been reported for APDS2 patients. Here, we describe a patient suffering from an APDS2 associated with a Smith–Magenis syndrome (SMS), a complex genetic disorder affecting, among others, neurological manifestations and review the literature describing neurodevelopmental impacts in APDS2 and other PIDs/monogenetic disorders associated with dysregulated PI3K signaling.

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Activated PI3Kδ syndrome, an immunodeficiency disorder, leads to sensorimotor deficits recapitulated in a murine model

Cited by 2 publications

References 102 publications

A novel automated approach for improving standardization of the marble burying test enables quantification of burying bouts and activity characteristics

A novel automated approach for improving standardization of the marble burying test enables quantification of burying bouts and activity characteristics

Two Monogenetic Disorders, Activated PI3-Kinase-δ Syndrome 2 and Smith–Magenis Syndrome, in One Patient: Case Report and a Literature Review of Neurodevelopmental Impact in Primary Immunodeficiencies Associated With Disturbed PI3K Signaling

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