Guoynes Caleigh D, Pavalko Grace, Sidorov Michael S
Children's National Hospital.
Res Sq. 2025 Feb 11:rs.3.rs-5953744. doi: 10.21203/rs.3.rs-5953744/v1.
Angelman syndrome (AS) is a single-gene neurodevelopmental disorder caused by loss of function of the maternal copy of the gene. Nearly all individuals with AS lack speech, resulting in major impacts on daily life for patients and caregivers. To evaluate new therapies for AS, it is crucial to have a mouse model that characterizes meaningful clinical features. Vocalizations are used in many contexts in mice, including pup retrieval, social interactions, courtship, and distress. Previous work in the mouse model of AS found abnormalities in the number of ultrasonic vocalizations (USVs) mice produced during pup isolation and same-sex social interactions. Here, we evaluated vocalizations during courtship and distress. Quantifying USVs in these contexts enables comparison of USVs in social (courtship) and non-social (distress) settings. In addition, we assessed the utility of incorporating USV testing into existing mouse behavioral assessments used to evaluate potential AS treatments.
We used a three-chamber social preference test for courtship vocalizations and a tail suspension test for distress vocalizations in adult wild-type (WT) and littermates, and quantified USV properties using the program DeepSqueak. Next, mice performed an established behavioral battery that included rotarod, open field, marble burying, and nest building. We used principal component analysis to evaluate the value of USV testing in the context of other behaviors.
In both social courtship and nonsocial distress behavioral paradigms, mice made fewer USVs compared to WT mice. Spectral properties of USVs were abnormal in mice on the courtship test but mostly typical on the distress test. Including USVs in the mouse behavior battery increased the distance between and WT clusters in principal component space.
mice have difficulty producing USVs in social and nonsocial contexts. Spectral properties of USVs are most impacted in the social courtship context. Adding USVs to the behavior battery may improve sensitivity to detect group differences and changes in communication.
天使综合征（AS）是一种单基因神经发育障碍，由该基因母本拷贝功能丧失引起。几乎所有AS患者都不会说话，这对患者及其照料者的日常生活产生了重大影响。为了评估AS的新疗法，拥有一个能体现有意义临床特征的小鼠模型至关重要。发声在小鼠的许多情境中都有应用，包括幼崽找回、社交互动、求偶和遇险。先前在AS小鼠模型中的研究发现，在幼崽隔离和同性社交互动期间，小鼠发出的超声波发声（USV）数量存在异常。在此，我们评估了求偶和遇险期间的发声情况。在这些情境中对USV进行量化，能够比较社交（求偶）和非社交（遇险）环境中的USV。此外，我们评估了将USV测试纳入用于评估潜在AS治疗方法的现有小鼠行为评估中的效用。
我们使用三室社交偏好测试来检测求偶发声，使用悬尾测试来检测成年野生型（WT）和同窝小鼠的遇险发声，并使用DeepSqueak程序对USV特性进行量化。接下来，小鼠进行了一系列既定的行为测试，包括转棒试验、旷场试验、埋珠试验和筑巢试验。我们使用主成分分析来评估在其他行为背景下USV测试的价值。
在社交求偶和非社交遇险行为范式中，与WT小鼠相比，AS小鼠发出的USV较少。在求偶测试中，AS小鼠的USV频谱特性异常，但在遇险测试中大多正常。将USV纳入小鼠行为测试组增加了主成分空间中AS组和WT组之间的距离。
AS小鼠在社交和非社交情境中发出USV存在困难。USV的频谱特性在社交求偶情境中受影响最大。将USV添加到行为测试组中可能会提高检测组间差异和交流变化的敏感性。
