Early Detection of Male-Predominant Phenotypes in the Pattern of Ultrasonic Vocalizations Emitted by Autism Spectrum Disorder Model (Crmp4-Knockout) Mice.

Early Detection of Male-Predominant Phenotypes in the Pattern of Ultrasonic Vocalizations Emitted by Autism Spectrum Disorder Model (Crmp4-Knockout) Mice.
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DOI:
10.3390/brainsci12050666
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发表时间:
2022-05-20
期刊:
影响因子:
3.3
通讯作者:
--
中科院分区:
医学4区
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--
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男性占优势是自闭症谱系障碍(ASD)的一个已知特征。虽然ASD小鼠模型可用于阐明与人类ASD相关的异常行为的潜在机制,但用于分析ASD发病机制中的性别差异的合适模型仍然不足。在此,我们使用了以男性为主的方式表现出ASD样表型的白细胞介素反应介体蛋白4(Crmp 4)基因敲除(KO)小鼠,并分析了超声发声(USVs),以检测出生后早期基因型和性别之间的潜在差异。我们记录了从野生型(WT)和Crmp 4-KO同窝仔中释放的分离诱导的USV,并比较了基因型和性别之间的USV总数。我们根据内部音高变化、长度和形状将USV分为10种类型,并根据基因型和性别比较了每种类型中USV的数量。雄性Crmp 4-KO小鼠显示USV总数减少。Crmp 4-KO减少了10种USV类型中7种的USV数量,并且雄性KO小鼠在7种类型中的3种中表现出比雌性更大的减少。本研究提供了一个合适的ASD动物模型和工具,以评估性别为基础的沟通缺陷在出生后早期,这两个将是有价值的阐明潜在的机制。
Male predominance is a known feature of autism spectrum disorder (ASD). Although ASD mouse models can be useful for elucidating mechanisms underlying abnormal behaviors relevant to human ASD, suitable models to analyze sex differences in ASD pathogenesis remain insufficient. Herein, we used collapsin response mediator protein 4 (Crmp4)-knockout (KO) mice exhibiting ASD-like phenotypes in a male-predominant manner and analyzed ultrasonic vocalizations (USVs) to detect potential differences between genotypes and sexes during the early postnatal period. We recorded isolation-induced USVs emitted from wild-type (WT) and Crmp4-KO littermates and compared the total number of USVs between genotypes and sexes. We classified USVs into 10 types based on internal pitch changes, lengths, and shapes and compared the number of USVs in each type by genotypes and sex. Male Crmp4-KO mice exhibited a reduction in the total number of USVs. Crmp4-KO decreased the number of USVs in 7 out of 10 USV types, and male KO mice exhibited a greater reduction than females in 3 of the 7 types. This study offers a suitable ASD animal model and tool for assessing sex-based communication deficits during the early postnatal period, both of which would be valuable for elucidating the underlying mechanism.
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