Rora, also known as retinoic acid receptor-related orphan receptor-α, is a transcription factor involved in multiple biological processes. It plays a role in regulating circadian rhythms, inflammation, metabolism, and cellular development. It is associated with pathways such as those related to cell differentiation, immune regulation, and tumorigenesis, making it biologically important [1,2,4]. Genetic models, like knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying its functions.

In a CD4-conditional Rora-knockout mouse model, Rora was found to be important for controlling lung inflammation induced by Nippostrongylus brasiliensis infection in CD4+ T cells, suggesting it is a negative regulator of the immune system [2]. In neuron-specific RORA null mice (a form of KO model), prenatal RORA deficiency mimicked maternal diabetes-mediated autism-like behavior, indicating RORA's role in autism-like phenotypes [3]. In Roraloxp/loxp Mx-1-Cre mice (a CKO model where Rora was deleted in hematopoietic cells post Pipc induction), Rora deficiency led to an accumulation of B cells, while its activation decreased B cell numbers, revealing its role in B cell development and Ph+ leukemogenesis [4].

In conclusion, Rora is crucial in various biological functions such as immune regulation, cell development, and in relation to diseases like autism-like phenotypes and leukemia. The use of Rora KO/CKO mouse models has significantly contributed to understanding its role in these specific disease areas and biological processes.

References:

1. Liu, Dandan, Wei, Benliang, Liang, Long, Liu, Hong, Liu, Jing. . The Circadian Clock Component RORA Increases Immunosurveillance in Melanoma by Inhibiting PD-L1 Expression. In Cancer research, 84, 2265-2281. doi:10.1158/0008-5472.CAN-23-3942. https://pubmed.ncbi.nlm.nih.gov/38718296/

2. Haim-Vilmovsky, Liora, Henriksson, Johan, Walker, Jennifer A, McKenzie, Andrew N J, Teichmann, Sarah A. 2021. Mapping Rora expression in resting and activated CD4+ T cells. In PloS one, 16, e0251233. doi:10.1371/journal.pone.0251233. https://pubmed.ncbi.nlm.nih.gov/34003838/

3. Yu, Hong, Niu, Yanbin, Jia, Guohua, Guo, Xiaoling, Yao, Paul. 2022. Maternal diabetes-mediated RORA suppression in mice contributes to autism-like offspring through inhibition of aromatase. In Communications biology, 5, 51. doi:10.1038/s42003-022-03005-8. https://pubmed.ncbi.nlm.nih.gov/35027651/

4. Li, Ning, Wang, Nan, He, Wei, Zhang, Haojian, Hu, Yiguo. 2022. The suppressive functions of Rora in B lineage cell proliferation and BCR/ABL1-induced B-ALL pathogenesis. In International journal of biological sciences, 18, 2277-2291. doi:10.7150/ijbs.68939. https://pubmed.ncbi.nlm.nih.gov/35414788/