Arl13b, an ADP-ribosylation factor-like GTPase, is a small regulatory GTPase highly enriched in cilia. It is involved in diverse biological processes such as cell-to-cell communication, energy homeostasis, and is associated with pathways like Hedgehog and VEGFA-VEGFR2 signaling. Genetically engineered mouse models have been crucial in studying its functions [1-7].

In mouse models, endothelial Arl13b regulates vascular development in the retina and brain, and its deficiency affects tumor angiogenesis and growth, as seen in glioma and melanoma models, by interacting with VEGFR2 [1]. In the context of energy homeostasis, mice with an engineered cilia-excluded Arl13B variant (Arl13bV358A) become obese, showing its role in preventing obesity [2]. Kidney-specific deletion of Arl13b leads to renal cysts, indicating its function in inhibiting renal cystogenesis during development [3,4]. In osteoblasts, knockdown of Arl13b affects cell proliferation, migration, osteogenesis, and mechanosensation [5]. In the male reproductive tract, deletion of Arl13b in efferent ductule epithelial cells compromises cilia architecture and function, leading to physiological imbalances [6]. In cerebral ischemia/reperfusion models, knockdown of Arl13b aggravates nerve injury, while its presence alleviates injury through the sonic hedgehog signaling pathway [7].

In conclusion, Arl13b is essential for multiple biological functions including vascular development, energy homeostasis, kidney development, bone formation, male reproductive tract physiology, and nerve protection during cerebral ischemia/reperfusion. Gene-knockout and conditional-knockout mouse models have been instrumental in uncovering its roles in diseases such as glioma, melanoma, obesity, kidney cystogenesis, and cerebral ischemia/reperfusion-related nerve damage, providing insights into potential therapeutic targets.

References:

1. Chen, Limin, Xie, Xinsheng, Wang, Tiantian, Chen, Ye-Guang, Luo, Shiwen. . ARL13B promotes angiogenesis and glioma growth by activating VEGFA-VEGFR2 signaling. In Neuro-oncology, 25, 871-885. doi:10.1093/neuonc/noac245. https://pubmed.ncbi.nlm.nih.gov/36322624/

2. Terry, Tiffany T, Gigante, Eduardo D, Alexandre, Coralie M, Vaisse, Christian, Caspary, Tamara. 2023. Ciliary ARL13B prevents obesity in mice. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.08.02.551695. https://pubmed.ncbi.nlm.nih.gov/37577625/

3. Van Sciver, Robert E, Long, Alyssa B, Katz, Harrison G, Gigante, Eduardo D, Caspary, Tamara. 2023. Ciliary ARL13B inhibits developmental kidney cystogenesis in mouse. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.02.08.527739. https://pubmed.ncbi.nlm.nih.gov/36798281/

4. Van Sciver, Robert E, Long, Alyssa B, Katz, Harrison G, Gigante, Eduardo D, Caspary, Tamara. 2023. Ciliary ARL13B inhibits developmental kidney cystogenesis in mouse. In Developmental biology, 500, 1-9. doi:10.1016/j.ydbio.2023.05.004. https://pubmed.ncbi.nlm.nih.gov/37209936/

5. Lin, Tingting, Sun, Yao. 2023. Arl13b promotes the proliferation, migration, osteogenesis, and mechanosensation of osteoblasts. In Tissue & cell, 82, 102088. doi:10.1016/j.tice.2023.102088. https://pubmed.ncbi.nlm.nih.gov/37058812/

6. Augière, Céline, Campolina-Silva, Gabriel, Vijayakumaran, Aaran, Mennella, Vito, Belleannée, Clémence. 2024. ARL13B controls male reproductive tract physiology through primary and Motile Cilia. In Communications biology, 7, 1318. doi:10.1038/s42003-024-07030-7. https://pubmed.ncbi.nlm.nih.gov/39397107/

7. Jiang, Lu, Yang, Shaonan, Deng, Ling, Chen, Sha, Dong, Zhi. 2024. ARL13B promotes cell cycle through the sonic hedgehog signaling pathway to alleviate nerve damage during cerebral ischemia/reperfusion in rats. In Biochemical pharmacology, 227, 116446. doi:10.1016/j.bcp.2024.116446. https://pubmed.ncbi.nlm.nih.gov/39038552/