Sex-specific role for the long noncoding RNA Pnky in mouse behavior.
Sex-specific role for the long noncoding RNA Pnky in mouse behavior.
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长非编码 RNA Pnky 在小鼠行为中的性别特异性作用。
DOI：
10.1101/2023.12.05.569777
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Lim,DanielA
中科院分区：
文献类型：
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作者：
Saha,Parna;Andersen,RebeccaE;Hong,SungJun;Gil,Eugene;Simms,Jeffrey;Lim,DanielA
特定长非编码 RNA (lncRNA) 的异常表达与认知和精神疾病有关。尽管现在已知越来越多的 lncRNA 可以调节神经细胞发育和功能，但被证明是动物行为基础的 lncRNA 相对较少。Pnky 是一种进化上保守的神经 lncRNA，调节大脑发育。使用小鼠遗传策略，我们证明 Pnky 在小鼠行为中具有性别特异性作用，并且该 lncRNA 可以通过反式功能来实现特定行为。 MalePnky 基因敲除小鼠在联想恐惧学习和记忆的范式中降低了情境泛化。在雌性 Pnky 基因敲除小鼠中，声音惊吓反应增强，这种行为在情感障碍中会发生改变。值得注意的是，来自细菌人工染色体转基因的 Pnky 表达降低了雌性 Pnky 基因敲除小鼠的声惊吓反应，这表明 Pnky 可以通过反式功能调节特定的动物行为。更广泛地说，这些研究说明了特定的 lncRNA 如何导致认知和情绪障碍。
The aberrant expression of specific long noncoding RNAs (lncRNAs) has been associated with cognitive and psychiatric disorders. Although a growing number of lncRNAs are now known to regulate neural cell development and function, relatively few lncRNAs have been shown to underlie animal behavior.Pnkyis an evolutionarily conserved, neural lncRNA that regulates brain development. Using mouse genetic strategies, we show thatPnkyhas sex-specific roles in mouse behavior and that this lncRNA can underlie specific behavior by functioning intrans. MalePnky-knockout mice have decreased context generalization in a paradigm of associative fear learning and memory. In femalePnky-knockout mice, there is an increase in the acoustic startle response, a behavior that is altered in affective disorders. Remarkably, expression ofPnkyfrom a bacterial artificial chromosome transgene decreases the acoustic startle response in femalePnky-knockout mice, demonstrating thatPnkycan modulate specific animal behavior by functioning intrans. More broadly, these studies illustrate how specific lncRNAs can underlie cognitive and mood disorders.