Generation of c-Fos knockout rats, and observation of their phenotype

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.

Automated summary

c-Fos is a useful marker gene of neuron activation for neuroscience and physiology research. Although c-Fos reporter knock-in (KI) mice have been used to investigate the mechanism and function of neural networks, performing surgical procedures on specific brain regions is challenging due to the small size of the mice. In contrast, rats have been extensively used in behavioral studies. This study successfully generated c-Fos-deficient rats using CRISPR/Cas, and observed similar abnormalities as observed in c-Fos knockout (KO) mice. The findings suggest that c-Fos gene in rats is expected to have the same function as that in mice.