A mouse model of 22q11.2 deletions: Molecular and behavioral signatures of Parkinson’s disease and schizophrenia

Akiko Sumitomo, Kouta Horike, Kazuko Hirai, Nancy Butcher, Erik Boot, Takeshi Sakurai, Frederick Nucifora, Anne S. Bassett, Akira Sawa, Toshifumi Tomoda

Research output: Contribution to journalArticle

Abstract

Individuals with chromosome 22q11.2 deletions are at increased risk of developing psychiatric conditions, most notably, schizophrenia (SZ). Recently, clinical studies have also implicated these recurrent 22q11.2 deletions with the risk of early-onset Parkinson’s disease (PD). Thus far, the multiple mouse models generated for 22q11.2 deletions have been studied primarily in the context of congenital cardiac, neurodevelopmental, and psychotic disorders. One of these is the Df1/+ model, in which SZ-associated and developmental abnormalities have been reported. We present the first evidence that the mouse model for the 22q11.2 deletion exhibits motor coordination deficits and molecular signatures (that is, elevated -synuclein expression) relevant to PD. Reducing the -synuclein gene dosage in Df1/+ mice ameliorated the motor deficits. Thus, this model of the 22q11.2 deletion shows signatures of both SZ and PD at the molecular and behavioral levels. In addition, both SZ-associated and PD-relevant deficits in the model were ameliorated by treatment with a rapamycin analog, CCI-779. We now posit the utility of 22q11.2 deletion mouse models in investigating the mechanisms of SZ- and PD-associated manifestations that could shed light on possible common pathways of these neuropsychiatric disorders.

Original languageEnglish (US)
Article numbereaar6637
JournalScience advances
Volume4
Issue number8
DOIs
StatePublished - Aug 15 2018

ASJC Scopus subject areas

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    Sumitomo, A., Horike, K., Hirai, K., Butcher, N., Boot, E., Sakurai, T., Nucifora, F., Bassett, A. S., Sawa, A., & Tomoda, T. (2018). A mouse model of 22q11.2 deletions: Molecular and behavioral signatures of Parkinson’s disease and schizophrenia. Science advances, 4(8), [eaar6637]. https://doi.org/10.1126/sciadv.aar6637