# Structure and Function of Neonatal Social Communication in Genetic Mouse Models of Autism

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2021 · $334,824

## Abstract

A critical step to improving our understanding of autism spectrum disorder (ASD) is to identify underlying
genetic and environmental risk factors. A number of rare copy number variants (CNVs) have emerged as
robust genetic risk factors for ASD. However, not all individuals exhibit ASD and the severity of ASD symptoms
varies among carriers of a CNV. Given that early therapeutic intervention attenuates symptoms, it is
reasonable to assume that early environmental factors also influence ASD symptoms later. However,
manipulation of the interplay between genetic and early environmental factors to identify mechanisms is
difficult in humans. Our team is uniquely positioned to experimentally address this issue. First, we have
identified atypical pup vocal call sequences of a genetic mouse model of ASD. To do so, our team applied a
set of sophisticated statistical tools. Second, our team developed innovative experimental tools and
demonstrated that such atypical pup call sequences induce less maternal approach. This observation shows
that neonatal vocalization is a means of social communication with mothers and suggests that it influences the
level of maternal care. Third, we found that enriched housing, an environmental manipulation known to reverse
the detrimental behavioral effects of maternal separation in mice, alters the expression and methylation of a
CNV-encoded gene in mouse brains. Capitalizing on these innovative methods and observations, we propose
to test our central hypothesis that CNVs disturb neonatal social communication with the mother and
this early experience exacerbates ASD-like behaviors via epigenetically modified expression of CNV-
encoded genes. We will use mouse models of paternal 15q11-13 duplication, 15q13.3 hemizygosity and
22q11.2 hemizygosity, as they represent three robust genetic risk factors for ASD. Use of multiple models will
allow us to determine common, as well as distinct roles of neonatal social communication in CNV-associated
ASD. We propose to achieve the following three Aims: Aim 1: Determine if CNVs result in atypical vocalization
structure during the neonatal period and if it is correlated with ASD-like behaviors at 2 months of age; Aim 2:
Determine the impact of atypical neonatal vocalization on maternal care; Aim 3: Measure the effect of altered
maternal care on the severity of ASD-like behaviors and CNV gene expression and epigenetic modification.
The outcomes of this project will reveal the interplay between genetic factors and neonatal social
communication with mothers resulting in the ultimate severity of ASD-like behaviors through epigenetic
mechanisms. The project has high translational value because it could provide a novel mechanistic base to
understand the gene-environment interaction underlying ASD.

## Key facts

- **NIH application ID:** 10220931
- **Project number:** 5R01DC015776-06
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Noboru Hiroi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $334,824
- **Award type:** 5
- **Project period:** 2017-08-21 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220931

## Citation

> US National Institutes of Health, RePORTER application 10220931, Structure and Function of Neonatal Social Communication in Genetic Mouse Models of Autism (5R01DC015776-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10220931. Licensed CC0.

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