Rhoa-KO Mouse

RhoA, short for Ras homolog gene family member A, is a small GTPase of the Rho family. It plays a pivotal role in regulating multiple signal transduction pathways, influencing diverse cellular functions such as cell survival, migration, adhesion, proliferation, and cytoskeletal dynamics [1,2]. The RhoA/ROCK signaling pathway is associated with numerous biological processes, including those in the nervous system [5,6]. Genetic models, like KO/CKO mouse models, are valuable for studying RhoA's functions.

Aberrant RhoA signaling has been implicated in neurodegenerative diseases such as Parkinson's, Alzheimer's, Huntington's, and amyotrophic lateral sclerosis. In Alzheimer's, the RhoA/ROCK signaling pathway promotes the disease's occurrence, for example, ROCK activation increases β -secretase activity and Aβ production, and Aβ further activates ROCK [1,6]. In cancer, RHOA may act as both an oncogene and a tumor suppressor, with mutations in RHOA identified in primary leukemia/lymphoma and gastric cancer [2,3,4]. In capillary malformation-arteriovenous malformation syndrome, loss of RASA1 function may lead to constitutive activation of RhoA signaling in endothelial cells, increasing vascular permeability [7]. Also, RhoA is crucial for myoblast fusion, as its absence in satellite cells prevents proper fusion during muscle regeneration and hypertrophy [8]. Additionally, RhoA has a role in DNA damage response, with components like ATM, FEN1, and ROS regulating its activation, and it mediates cell cycle arrest [9].

In conclusion, RhoA is essential in regulating various cellular functions and signaling pathways. Model-based research, especially KO/CKO mouse models, has revealed its significance in neurodegenerative diseases, cancers, vascular syndromes, muscle regeneration, and DNA damage response. Understanding RhoA's functions provides insights into the mechanisms of these biological processes and diseases, potentially guiding the development of new therapeutic strategies.

References:

1. Schmidt, Sissel Ida, Blaabjerg, Morten, Freude, Kristine, Meyer, Morten. 2022. RhoA Signaling in Neurodegenerative Diseases. In Cells, 11, . doi:10.3390/cells11091520. https://pubmed.ncbi.nlm.nih.gov/35563826/

2. Santos, Juliana Carvalho, Profitós-Pelejà, Núria, Sánchez-Vinces, Salvador, Roué, Gaël. 2023. RHOA Therapeutic Targeting in Hematological Cancers. In Cells, 12, . doi:10.3390/cells12030433. https://pubmed.ncbi.nlm.nih.gov/36766776/

3. Schaefer, Antje, Der, Channing J. 2022. RHOA takes the RHOad less traveled to cancer. In Trends in cancer, 8, 655-669. doi:10.1016/j.trecan.2022.04.005. https://pubmed.ncbi.nlm.nih.gov/35568648/

4. Benton, Dorothy, Chernoff, Jonathan. 2023. RHOA drivers take alternate routes in gastric cancer. In Science signaling, 16, eadk9171. doi:10.1126/scisignal.adk9171. https://pubmed.ncbi.nlm.nih.gov/38113334/

5. Lu, Weizhuo, Chen, Zhiwu, Wen, Jiyue. 2021. RhoA/ROCK signaling pathway and astrocytes in ischemic stroke. In Metabolic brain disease, 36, 1101-1108. doi:10.1007/s11011-021-00709-4. https://pubmed.ncbi.nlm.nih.gov/33745103/

6. Cai, RuoLan, Wang, YangYang, Huang, ZhenTing, Yu, Changyin, Cai, Zhiyou. 2021. Role of RhoA/ROCK signaling in Alzheimer's disease. In Behavioural brain research, 414, 113481. doi:10.1016/j.bbr.2021.113481. https://pubmed.ncbi.nlm.nih.gov/34302876/

7. Eisa-Beygi, Shahram, Vo, Nghia Jack, Link, Brian A. 2020. RhoA activation-mediated vascular permeability in capillary malformation-arteriovenous malformation syndrome: a hypothesis. In Drug discovery today, 26, 1790-1793. doi:10.1016/j.drudis.2020.12.012. https://pubmed.ncbi.nlm.nih.gov/33358701/

8. Noviello, Chiara, Kobon, Kassandra, Randrianarison-Huetz, Voahangy, Falcone, Sestina, Sotiropoulos, Athanassia. 2023. RhoA Is a Crucial Regulator of Myoblast Fusion. In Cells, 12, . doi:10.3390/cells12232673. https://pubmed.ncbi.nlm.nih.gov/38067102/

9. Cheng, Chibin, Seen, Daniel, Zheng, Chunwen, Zeng, Ruijie, Li, Enmin. 2021. Role of Small GTPase RhoA in DNA Damage Response. In Biomolecules, 11, . doi:10.3390/biom11020212. https://pubmed.ncbi.nlm.nih.gov/33546351/