Single-nucleus RNA sequencing of the prefrontal cortex from mice lacking glutaminase 1 in CamKIIa-positive neurons and control mice

Autism spectrum disorder (ASD) is a heterogeneous group of disorders with shared diagnostic phenotypes, such as reduced interest in social interaction and communication, and increased stereotyped or restricted interests and behaviors. Little is known about the involvement of alterations of glutaminase 1 (Gls1, an enzyme that catalyzes the hydrolysis of glutamine into glutamate) in the pathogenesis of ASD. To investigate the role of Gls1 in forebrain neurons , we generated conditional mouse mutants with loss of Gls1 in forebrain CamKIIα-Cre positive neurons by crossing Gls1flox/flox mice with CamKIIαcre mice. Conditional mouse mutants with loss of Gls1 in forebrain CamKIIα-Cre positive neurons were generated by crossing Gls1flox/flox mice with CamKIIαcre mice. Mosaic homozygous Gls1 mutant (CamKIIαCre;Gls1flox/flox) mice were not viable. Only mosaic heterozygous Gls1 mice (CamKIIαCre;Gls1+/flox mice, referred to as Gls1_CamKIIαCre mice) and their littermate CamKIIαCre;Gls1+/+ mice (referred to as control mice) were used in this study. Cells from the prefrontal cortex of both groups were isolated for Single-Nucleus RNA sequencing. Three animals were included for each group.

自闭症谱系障碍（Autism spectrum disorder, ASD）是一类具有共同诊断表型的异质性疾病群，典型临床表现包括社交互动与沟通兴趣减退、刻板或受限的兴趣与行为增多。目前学界对谷氨酰胺酶1（glutaminase 1, Gls1，一种催化谷氨酰胺水解为谷氨酸的酶）的异常在ASD发病机制中的参与机制尚不明确。为探究Gls1在前脑神经元中的功能，我们将Gls1 flox/flox小鼠与CamKIIαcre小鼠杂交，构建了在前脑CamKIIα-Cre阳性神经元中特异性敲除Gls1的条件性小鼠突变体。研究显示，镶嵌型纯合Gls1突变小鼠（CamKIIαCre;Gls1flox/flox）无法存活，本研究仅纳入镶嵌型杂合Gls1小鼠（CamKIIαCre;Gls1+/flox，简称Gls1_CamKIIαCre小鼠）及其同窝野生型对照小鼠（CamKIIαCre;Gls1+/+，简称对照小鼠）。我们分离两组小鼠的前额叶皮层细胞进行单细胞核RNA测序，每组包含3只实验动物。