Younger Skyler, Boutros Sydney, Cargnin Francesca, Jeon Shin, Lee Jae W, Lee Soo-Kyung, Raber Jacob
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States.
Spark Therapeutics, Inc., Philadelphia, PA, United States.
Front Pharmacol. 2022 Jun 8;13:927296. doi: 10.3389/fphar.2022.927296. eCollection 2022.
FOXG1 syndrome (FS, aka a congenital variant of Rett syndrome) is a recently defined rare and devastating neurodevelopmental disorder characterized by various symptoms, including severe intellectual disability, autistic features, involuntary, and continuous jerky movements, feeding problems, sleep disturbances, seizures, irritability, and excessive crying. FS results from mutations in a single allele of the FOXG1 gene, leading to impaired FOXG1 function. Therefore, in establishing mouse models for FS, it is important to test if heterozygous (HET) mutation in the Foxg1 gene, mimicking genotypes of the human FS individuals, also manifests phenotypes similar to their symptoms. We analyzed HET mice with a null mutation allele in a single copy of Foxg1, and found that they show various phenotypes resembling the symptoms of the human FS individuals. These include increased anxiety in the open field as well as impairment in object recognition, motor coordination, and fear learning and contextual and cued fear memory. Our results suggest that Foxg1 HET mice recapitulate at least some symptoms of the human FS individuals.
FOXG1综合征（FS，又称雷特综合征的先天性变异型）是一种最近定义的罕见且严重的神经发育障碍，其特征为多种症状，包括严重智力残疾、自闭症特征、不自主且持续的抽搐动作、喂养问题、睡眠障碍、癫痫发作、易激惹和过度哭闹。FS由FOXG1基因的单个等位基因突变引起，导致FOXG1功能受损。因此，在建立FS的小鼠模型时，重要的是测试模拟人类FS个体基因型的Foxg1基因杂合（HET）突变是否也表现出与其症状相似的表型。我们分析了Foxg1单拷贝中带有无效突变等位基因的HET小鼠，发现它们表现出各种类似于人类FS个体症状的表型。这些包括在旷场试验中焦虑增加以及物体识别、运动协调、恐惧学习以及情境和线索恐惧记忆方面的损伤。我们的结果表明，Foxg1 HET小鼠至少重现了人类FS个体的一些症状。
