**3. Rat Models**

Rats are the generally used experimental animal the same as mice and have some advantages compared with mice such as large body and tissue size and physiological properties similar to those in humans. Despite the advantages, mice have been more frequently used than rats; this is probably due to, except for higher experimental costs than mice, the technical difficulty of creating KO/KI rats. However, genome-editing technologies, i.e., zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPRs)-associated proteins 9 (CRISPR-Cas9), made it possible to also create KO/KI rats easily. In 2009, Geurts et al. first reported the creation of KO rats by ZFN [100]. Thereafter, a growing body of literature has emerged in the last decade reporting phenotypes of KO/KI rats including genetic hypertensive models as below [101,102].
