# Cell-type-specific NRXN1alpha alternative splicing changes in psychiatric disease

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $809,441

## Abstract

PROJECT SUMMARY
Schizophrenia, bipolar disorder and autism are common and debilitating neurodevelopmental disorders that
together affect more than 5 million Americans. Despite more than fifty years of research, no cures exist and the
standard of treatment remains unsatisfactory. Heterozygous mutations of neurexin-1 (NRXN1) have been
repeatedly associated with schizophrenia (SZ) and autism spectrum disorder (ASD). The clinical presentations
of NRXN1+/- mutations (including diagnosis, severity, prognosis and age-of-onset) in affected patients are
diverse and the genetic mechanism affecting the penetrance of these mutations remains unknown. Moreover,
mouse models do not permit researchers to study how and why some NRXN1+/- deletions have more
deleterious effects in patients. Our objective is to resolve how NRXN1+/- deletions perturb the NRXN1 isoform
repertoire and impact neuronal maturation and synaptic function. Our preliminary data defined the NRXN1
alternative splice repertoire in control fetal and adult cortical tissue, and compared this to human induced
pluripotent stem cell (hiPSC)-derived neurons from NRXN1+/- cases and controls. Here, we propose to
evaluate the effect of experimental manipulation of the NRXN1 isoform repertoire in both control and NRXN1+/-
patient-derived excitatory and inhibitory neurons. Ultimately, we hope to directly correlate genomic and
functional deficits across increasingly refined populations of NRXN1+/- patient-derived neurons.

## Key facts

- **NIH application ID:** 9980504
- **Project number:** 5R01MH121074-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Kristen Jennifer Brennand
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $809,441
- **Award type:** 5
- **Project period:** 2019-07-18 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980504

## Citation

> US National Institutes of Health, RePORTER application 9980504, Cell-type-specific NRXN1alpha alternative splicing changes in psychiatric disease (5R01MH121074-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980504. Licensed CC0.

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