Robo1-flox Mouse

Robo1, short for roundabout homolog 1, is a transmembrane receptor. It plays a crucial role in cell growth, migration, and axon guidance, often through interaction with its ligand, Slit proteins. The Slit2-Robo1 signaling pathway is involved in multiple biological processes and diseases [1,2,4,5,6,8]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, have been valuable in studying Robo1's functions.

In liver fibrosis, Robo1 activation promotes liver injury and fibrosis via hepatic stellate cell (HSC) activation. Mice with Slit2 over-expression (Slit2-Tg) were more vulnerable to CCl4-induced liver injury and fibrosis, while Robo1/2(+/-) double heterozygotes showed attenuated liver injury and fibrosis [1]. In pressure-overload-induced cardiac hypertrophy, cardiomyocyte-specific deletion of ROBO1 preserved left ventricular function and abrogated hypertrophy [2]. In glioblastoma, targeting ROBO1 with CAR T cells doubled median survival in recurrent GBM models [3]. In pancreatic ductal adenocarcinoma, a neutralizing antibody against ROBO1 significantly attenuated liver metastasis by disrupting co-adaptation [6]. In epilepsy, Robo1 knockdown in a mouse model prolonged seizure latency and reduced seizure grade, suggesting its role in epileptogenesis [7].

In conclusion, Robo1 is essential in regulating cell growth, migration, and axon guidance. Studies using KO/CKO mouse models have revealed its role in various diseases including liver fibrosis, cardiac hypertrophy, glioblastoma, pancreatic cancer liver metastasis, and epilepsy. These findings provide insights into potential therapeutic strategies targeting Robo1 for these diseases.