Hulbert Samuel W, Jiang Yong-Hui
Department of Neurobiology, School of Medicine, Duke University, Durham, NC, 27710, USA.
Department of Pediatrics, School of Medicine, Duke University, Durham, NC, 27710, USA.
Neurosci Bull. 2017 Apr;33(2):205-218. doi: 10.1007/s12264-017-0112-7. Epub 2017 Mar 7.
Transgenic mice carrying mutations that cause Autism Spectrum Disorders (ASDs) continue to be valuable for determining the molecular underpinnings of the disorders. Recently, researchers have taken advantage of such models combined with Cre-loxP and similar systems to manipulate gene expression over space and time. Thus, a clearer picture is starting to emerge of the cell types, circuits, brain regions, and developmental time periods underlying ASDs. ASD-causing mutations have been restricted to or rescued specifically in excitatory or inhibitory neurons, different neurotransmitter systems, and cells specific to the forebrain or cerebellum. In addition, mutations have been induced or corrected in adult mice, providing some evidence for the plasticity and reversibility of core ASD symptoms. The limited availability of Cre lines that are highly specific to certain cell types or time periods provides a challenge to determining the cellular and circuitry bases of autism, but other technological advances may eventually overcome this obstacle.
携带导致自闭症谱系障碍(ASD)突变的转基因小鼠对于确定这些疾病的分子基础仍然具有重要价值。最近,研究人员利用此类模型结合Cre-loxP及类似系统,在空间和时间上操纵基因表达。因此,关于ASD背后的细胞类型、神经回路、脑区和发育时间段的更清晰图景开始浮现。导致ASD的突变已被限制在兴奋性或抑制性神经元、不同神经递质系统以及前脑或小脑特有的细胞中,或在这些细胞中得到特异性挽救。此外,已在成年小鼠中诱导或纠正突变,为ASD核心症状的可塑性和可逆性提供了一些证据。高度特异性针对某些细胞类型或时间段的Cre品系数量有限,这给确定自闭症的细胞和神经回路基础带来了挑战,但其他技术进步最终可能克服这一障碍。