RORB, also known as RAR-related orphan receptor B, is a developmental transcription factor belonging to the nuclear receptor family. It plays important roles in cell fate specification in the retina, cortical layer formation, and is involved in regulating neural development and function. It may participate in pathways related to the unfolded protein response and endoplasmic reticulum stress [8].

In rabbits, a loss-of-function mutation in RORB disrupts saltatorial locomotion. This mutation leads to a reduction of RORB-positive neurons in the spinal cord and defects in the differentiation of spinal cord interneurons [7]. In mice, loss of RORB causes disorganized retina layers, postnatal degeneration, and production of immature cone photoreceptors, as well as hyperflexion or "high-stepping" of rear limbs due to reduced presynaptic inhibition by Rorb-expressing inhibitory interneurons of the spinal cord [8]. In human studies, RORB has been associated with endometriosis, Alzheimer's disease, islet dysfunction, and epilepsy. In endometriosis, it may be a potential biomarker [1]. In Alzheimer's disease, it is a marker of selectively vulnerable excitatory neurons in the entorhinal cortex and its variants may decrease the risk of AD [2,3]. In pancreatic β cells, RORB is part of the molecular cascade regulating insulin secretion [4]. In epilepsy, heterozygous variants in RORB are associated with susceptibility to idiopathic generalized epilepsy, and the phenotype often associates absence seizures with mild-to-moderate intellectual disability [5,6].

In conclusion, RORB is crucial for normal neural development, locomotion, and retinal function. Through gene-knockout or conditional-knockout mouse models, its role in various biological processes has been revealed. In humans, it is associated with multiple diseases, providing potential targets for disease diagnosis and treatment. These model-based studies have significantly contributed to understanding the role of RORB in specific disease areas such as Alzheimer's, epilepsy, and endometriosis.

References:

1. Geng, Rong, Huang, Xiaobin, Li, Linxi, Zheng, Yuhua, Guo, Xiaoling. 2022. Gene expression analysis in endometriosis: Immunopathology insights, transcription factors and therapeutic targets. In Frontiers in immunology, 13, 1037504. doi:10.3389/fimmu.2022.1037504. https://pubmed.ncbi.nlm.nih.gov/36532015/

2. Leng, Kun, Li, Emmy, Eser, Rana, Grinberg, Lea T, Kampmann, Martin. 2021. Molecular characterization of selectively vulnerable neurons in Alzheimer's disease. In Nature neuroscience, 24, 276-287. doi:10.1038/s41593-020-00764-7. https://pubmed.ncbi.nlm.nih.gov/33432193/

3. Lehrer, Steven, Rheinstein, Peter H. 2023. RORB, an Alzheimer's disease susceptibility gene, is associated with viral encephalitis, an Alzheimer's disease risk factor. In Clinical neurology and neurosurgery, 233, 107984. doi:10.1016/j.clineuro.2023.107984. https://pubmed.ncbi.nlm.nih.gov/37734269/

4. Taneera, Jalal, Mohammed, Abdul Khader, Dhaiban, Sarah, Sulaiman, Nabil, Salehi, Albert. 2019. RORB and RORC associate with human islet dysfunction and inhibit insulin secretion in INS-1 cells. In Islets, 11, 10-20. doi:10.1080/19382014.2019.1566684. https://pubmed.ncbi.nlm.nih.gov/30762474/

5. Gokce-Samar, Zeynep, Vetro, Annalisa, De Bellescize, Julitta, Guerrini, Renzo, Lesca, Gaetan. 2023. Molecular and Phenotypic Characterization of the RORB-Related Disorder. In Neurology, 102, e207945. doi:10.1212/WNL.0000000000207945. https://pubmed.ncbi.nlm.nih.gov/38165337/

6. Sadleir, Lynette G, de Valles-Ibáñez, Guillem, King, Chontelle, Mefford, Heather C, Scheffer, Ingrid E. 2020. Inherited RORB pathogenic variants: Overlap of photosensitive genetic generalized and occipital lobe epilepsy. In Epilepsia, 61, e23-e29. doi:10.1111/epi.16475. https://pubmed.ncbi.nlm.nih.gov/32162308/

7. Carneiro, Miguel, Vieillard, Jennifer, Andrade, Pedro, Kullander, Klas, Andersson, Leif. 2021. A loss-of-function mutation in RORB disrupts saltatorial locomotion in rabbits. In PLoS genetics, 17, e1009429. doi:10.1371/journal.pgen.1009429. https://pubmed.ncbi.nlm.nih.gov/33764968/

8. Murray, George C, Bubier, Jason A, Zinder, Oraya J, Burgess, Robert W, Tadenev, Abigail L D. . An allelic series of spontaneous Rorb mutant mice exhibit a gait phenotype, changes in retina morphology and behavior, and gene expression signatures associated with the unfolded protein response. In G3 (Bethesda, Md.), 13, . doi:10.1093/g3journal/jkad131. https://pubmed.ncbi.nlm.nih.gov/37300435/