Neuronal deletion of Gtf2i results in developmental microglial alterations in a mouse model related to Williams syndrome

Ela Bar, Inbar Fischer, May Rokach, Galit Elad-Sfadia, Sophie Shirenova, Omer Ophir, Sari Schokoroy Trangle, Eitan Okun*, Boaz Barak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Williams syndrome (WS) is a genetic neurodevelopmental disorder caused by a heterozygous microdeletion, characterized by hypersociability and unique neurocognitive abnormalities. Of the deleted genes, GTF2I has been linked to hypersociability in WS. We have recently shown that Gtf2i deletion from forebrain excitatory neurons, referred to as Gtf2i conditional knockout (cKO) mice leads to multi-faceted myelination deficits associated with the social behaviors affected in WS. These deficits were potentially mediated also by microglia, as they present a close relationship with oligodendrocytes. To study the impact of altered myelination, we characterized these mice in terms of microglia over the course of development. In postnatal day 30 (P30) Gtf2i cKO mice, cortical microglia displayed a more ramified state, as compared with wild type (controls). However, postnatal day 4 (P4) microglia exhibited high proliferation rates and an elevated activation state, demonstrating altered properties related to activation and inflammation in Gtf2i cKO mice compared with control. Intriguingly, P4 Gtf2i cKO-derived microglial cells exhibited significantly elevated myelin phagocytosis in vitro compared to control mice. Lastly, systemic injection of clemastine to P4 Gtf2i cKO and control mice until P30, led to a significant interaction between genotypes and treatments on the expression levels of the phagocytic marker CD68, and a significant reduction of the macrophage/microglial marker Iba1 transcript levels in the cortex of the Gtf2i cKO treated mice. Our data thus implicate microglia as important players in WS, and that early postnatal manipulation of microglia might be beneficial in treating inflammatory and myelin-related pathologies.

Original languageEnglish
Pages (from-to)1117-1135
Number of pages19
Issue number6
StatePublished - Jun 2024


FundersFunder number
National Institute of Psychobiology in Israel
Israel Science Foundation2305/20
Israel Science Foundation


    • Gtf2i
    • Williams syndrome
    • clemastine
    • microglia
    • microglial activation
    • myelin
    • neurodevelopmental disorders


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