# Role of the Sez6 family in synapse pruning

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2020 · $192,500

## Abstract

Complement promotes synaptic pruning by glia in order to refine neural circuits during
development, but may also pathologically destroy mature, essential synapses in the context of
neuroinflammation. Immune dysfunction and an imbalance in synaptic pruning have been
implicated in autism spectrum disorder (ASD), and recent studies suggest that dysregulation
of complement may be connected. The central hypothesis to be tested in this application is that
the Sez6 gene family, whose members have been identified as ASD susceptibility genes, are
novel, synaptically localized, complement regulators that are required to prevent aberrant
synaptic pruning related to ASD. In Aim 1, we will define the complement regulatory properties
of Sez6, Sez6L, and Sez6L2 using standard complement assays. We will then investigate
whether the Sez6 family can prevent complement deposition at synapses in vitro. In Aim 2, we
will use the 16p11.2 deletion mouse model of autism, in which Sez6L2 is lost along with other
genes, to determine if enhanced complement dependent synapse pruning occurs at
retinogeniculate synapses in the visual system. A Sez6L2 knockout will also be tested in order
to validate findings and confirm the importance of SezL2 to the 16p11.2 phenotype. In
aggregate, we expect the data obtained from these experiments to advance our understanding
of the role of Sez6 proteins in mechanisms underlying complement-mediated synapse
elimination during development that may explain how this gene family contributes susceptibility
to ASD.

## Key facts

- **NIH application ID:** 9891120
- **Project number:** 5R21NS111255-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** JENNETTA W HAMMOND
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,500
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891120

## Citation

> US National Institutes of Health, RePORTER application 9891120, Role of the Sez6 family in synapse pruning (5R21NS111255-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9891120. Licensed CC0.

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