Arl2bp, encoding the ADP-Ribosylation Factor Like 2 Binding Protein, is a ciliary gene. Cilia are evolutionarily conserved structures with diverse biological roles, and Arl2bp is crucial for ciliary microtubule structure maintenance. It is associated with ciliopathy-related pathways and is of great biological importance in processes like ciliogenesis [2,3,4]. Mouse models, especially knockout (KO) models, have been instrumental in studying Arl2bp.

In KO mouse models, spermiogenesis is impaired, leading to abnormally shaped sperm heads, shortened and mis-assembled tails, and loss of axonemal doublets. The mice also show enlarged brain ventricles and situs inversus. Delayed depolymerization of primary cilia is observed in mouse embryonic fibroblasts from knockout animals. In the context of photoreceptors, KO mice display early and progressive reduction in visual response, with disorganized outer segments, vertically aligned disks, shortened axonemes, and impaired ciliary doublet microtubule structure [2,3].

In conclusion, Arl2bp is essential for the structural maintenance of cilia and sperm flagellum. Its deficiency leads to syndromic ciliopathy, manifested in phenotypes such as retinitis pigmentosa, situs inversus, male infertility, and associated with olfactory dysfunction in humans. The study of Arl2bp KO mouse models has significantly contributed to understanding the role of Arl2bp in these disease-related processes [1,2,3].

References:

1. Zhu, Tian, Li, Hui, Wei, Xing, Sun, Zixi, Sui, Ruifang. 2022. Novel homozygous variant in ARL2BP associated with retinitis pigmentosa, situs inversus, and male infertility in a Chinese patient. In Clinical genetics, 103, 472-477. doi:10.1111/cge.14278. https://pubmed.ncbi.nlm.nih.gov/36507858/

2. Moye, Abigail R, Bedoni, Nicola, Cunningham, Jessica G, Rivolta, Carlo, Ramamurthy, Visvanathan. 2019. Mutations in ARL2BP, a protein required for ciliary microtubule structure, cause syndromic male infertility in humans and mice. In PLoS genetics, 15, e1008315. doi:10.1371/journal.pgen.1008315. https://pubmed.ncbi.nlm.nih.gov/31425546/

3. Moye, Abigail R, Singh, Ratnesh, Kimler, Victoria A, Goldberg, Andrew F X, Ramamurthy, Visvanathan. 2018. ARL2BP, a protein linked to retinitis pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure. In Molecular biology of the cell, 29, 1590-1598. doi:10.1091/mbc.E18-01-0040. https://pubmed.ncbi.nlm.nih.gov/29718757/

4. Davidson, Alice E, Schwarz, Nele, Zelinger, Lina, Sharon, Dror, Webster, Andrew R. 2013. Mutations in ARL2BP, encoding ADP-ribosylation-factor-like 2 binding protein, cause autosomal-recessive retinitis pigmentosa. In American journal of human genetics, 93, 321-9. doi:10.1016/j.ajhg.2013.06.003. https://pubmed.ncbi.nlm.nih.gov/23849777/