Division of Integrative Physiology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.
Advanced Medicine Innovation and Clinical Research Center, Tottori University Hospital, 36-1 Nishi-cho, Yonago, Tottori 683-8504, Japan.
Exp Anim. 2023 Feb 21;72(1):95-102. doi: 10.1538/expanim.22-0077. Epub 2022 Oct 11.
c-Fos is a useful marker gene of neuron activation for neuroscience and physiology research. The mechanism and function of neural networks have been elucidated using c-Fos reporter knock-in (KI) mice, but the small size of the mice makes it difficult to perform surgical procedures on specific brain regions. On the other hand, there is a large amount of accumulated data on behavioral studies using rats. Thus, the generation of c-Fos reporter rat is expected, but it is difficult to generate gene-modified rats. Furthermore, c-Fos gene abnormality is expected to be severe in rats, as shown in homozygous of c-Fos knockout (KO) mouse, but such analysis has rarely been performed and is not certain. This study generated c-Fos-deficient rats using CRISPR/Cas, with 1067 bp deletion including exon 1 of the c-Fos gene. Homozygous c-Fos KO rats had growth latency and the same tooth and bone abnormality as homozygous c-Fos KO mice but not heterozygous c-Fos KO rats. Therefore, the c-Fos gene in rats is expected to have the same function as that in mice, and the generation of c-Fos reporter KI rats is further anticipated.
c-Fos 是神经科学和生理学研究中神经元激活的有用标记基因。利用 c-Fos 报告基因敲入 (KI) 小鼠阐明了神经网络的机制和功能，但小鼠体型小，使得对特定脑区进行手术变得困难。另一方面，使用大鼠进行行为研究积累了大量数据。因此，预计会产生 c-Fos 报告基因大鼠，但很难产生基因修饰大鼠。此外，如 c-Fos 基因敲除 (KO) 小鼠的纯合子所示，大鼠的 c-Fos 基因异常预计会很严重，但这种分析很少进行，也不确定。本研究使用 CRISPR/Cas 产生了 c-Fos 缺失的大鼠，该基因缺失包括 c-Fos 基因外显子 1 的 1067bp。c-Fos KO 纯合子大鼠的生长潜伏期以及牙齿和骨骼异常与 c-Fos KO 小鼠的纯合子相同，但与 c-Fos KO 大鼠的杂合子不同。因此，预计大鼠中的 c-Fos 基因与小鼠中的 c-Fos 基因具有相同的功能，并进一步预期生成 c-Fos 报告基因 KI 大鼠。
