Mammalian genomes include many maternally and paternally imprinted genes. Most of these are also expressed in the brain, and several have been implicated in regulating specific behavioral traits. Here, we have used a knockout approach to study the function of Peg13, a gene that codes for a fast-evolving lncRNA (long noncoding RNA) and is part of a complex of imprinted genes on chromosome 15 in mice and chromosome 8 in humans. Mice lacking the 3′ half of the transcript look morphologically wild-type but show distinct behavioral differences. They lose interest in the opposite sex, instead displaying a preference for wild-type animals of the same sex. Further, they show a higher level of anxiety, lowered activity and curiosity, and a deficiency in pup retrieval behavior. Brain RNA expression analysis reveals that genes involved in the serotonergic system, formation of glutamatergic synapses, olfactory processing, and estrogen signaling—as well as more than half of the other known imprinted genes—show significant expression changes in Peg13-deficient mice. Intriguingly, these pathways are differentially affected in the sexes, resulting in male and female brains of Peg13-deficient mice differing more from each other than those of wild-type mice. We conclude that Peg13 is part of a developmental pathway that regulates the neurobiology of social and sexual interactions.

哺乳动物基因组包括许多母系和父系印记基因。其中大多数也在大脑中表达，其中一些与调节特定行为特征有关。在这里，我们使用敲除方法来研究Peg13的功能，Peg13 是一种编码快速进化的 lncRNA（长非编码 RNA）的基因，是小鼠 15 号染色体和人类 8 号染色体上印记基因复合体的一部分。缺乏转录本 3' 部分的小鼠在形态上看起来是野生型，但表现出明显的行为差异。他们对异性失去兴趣，反而表现出对同性野生动物的偏好。此外，它们表现出较高程度的焦虑、较低的活动和好奇心以及幼犬检索行为的缺陷。大脑RNA表达分析表明，参与血清素能系统、谷氨酸能突触形成、嗅觉处理和雌激素信号传导的基因以及超过一半的其他已知印记基因在Peg13缺陷小鼠中表现出显着的表达变化。有趣的是，这些通路在性别中受到不同的影响，导致Peg13缺陷小鼠的雄性和雌性大脑之间的差异比野生型小鼠更大。我们得出的结论是，Peg13是调节社交和性互动神经生物学的发育途径的一部分。