Bbs5, short for Bardet-Biedl syndrome 5, is one of the eight subunits forming the BBSome protein complex. The BBSome is involved in protein trafficking within the cilia, a process crucial for cilia-mediated signal transduction [2,5]. Cilia are important sensory and signaling compartments, and their proper function is essential for various biological processes, so Bbs5 is of great biological significance. Gene knockout (KO) and conditional knockout (CKO) mouse models have been valuable for studying Bbs5.

In Bbs5 -/- mice, there is a significant loss of nuclei in the outer nuclear layer of the retina, accompanied by increased cell death and complete loss of cone photoreceptor function. Cone-specific proteins are mislocalized, and outer segment disk orientation is abnormal, suggesting Bbs5's role in mediating specific photoreceptor protein cargo transport in the retina [1]. Bbs5 -/- mice also develop a complex phenotype including increased pre-weaning lethality, craniofacial and skeletal defects, ventriculomegaly, infertility, and pituitary anomalies. Male fertility defects, ventriculomegaly, and pituitary abnormalities are developmentally-originated, while obesity occurs independent of the age of Bbs5 loss [3].

In conclusion, Bbs5 is essential for cilia-related protein trafficking. KO mouse models have revealed its role in maintaining retinal function, especially in cone photoreceptor protein transport, as well as its impact on development and homeostasis, including aspects like fertility, craniofacial and skeletal development, and body weight regulation. Mutations in Bbs5 are associated with ciliopathy-related disorders such as Bardet-Biedl syndrome [1,2,3,4,6].

References:

1. Bales, Katie L, Bentley, Melissa R, Croyle, Mandy J, Yoder, Bradley K, Gross, Alecia K. . BBSome Component BBS5 Is Required for Cone Photoreceptor Protein Trafficking and Outer Segment Maintenance. In Investigative ophthalmology & visual science, 61, 17. doi:10.1167/iovs.61.10.17. https://pubmed.ncbi.nlm.nih.gov/32776140/

2. Karam, Adella, Delvallée, Clarisse, Estrada-Cuzcano, Alejandro, Dollfus, Hélène, Muller, Jean. 2023. WGS Revealed Novel BBS5 Pathogenic Variants, Missed by WES, Causing Ciliary Structure and Function Defects. In International journal of molecular sciences, 24, . doi:10.3390/ijms24108729. https://pubmed.ncbi.nlm.nih.gov/37240074/

3. Bentley-Ford, Melissa R, Engle, Staci E, Clearman, Kelsey R, Berbari, Nicolas F, Yoder, Bradley K. . A mouse model of BBS identifies developmental and homeostatic effects of BBS5 mutation and identifies novel pituitary abnormalities. In Human molecular genetics, 30, 234-246. doi:10.1093/hmg/ddab039. https://pubmed.ncbi.nlm.nih.gov/33560420/

4. Torrefranca, Aramis B, Santiago, Alvina Pauline D, Lingao, Michelle D, Racoma, Marie Julianne C. 2020. Novel compound heterozygous pathogenic BBS5 variants in Filipino siblings with Bardet-Biedl syndrome (BBS). In Ophthalmic genetics, 41, 621-624. doi:10.1080/13816810.2020.1810282. https://pubmed.ncbi.nlm.nih.gov/32811249/

5. Hey, Caroline Amalie Brunbjerg, Larsen, Lasse Jonsgaard, Tümer, Zeynep, Hjortshøj, Tina Duelund, Møller, Lisbeth Birk. 2019. Generation and characterization of three isogenic induced pluripotent stem cell lines from a patient with Bardet-Biedl syndrome and homozygous for the BBS5 variant. In Stem cell research, 41, 101594. doi:10.1016/j.scr.2019.101594. https://pubmed.ncbi.nlm.nih.gov/31760295/

6. Imani, Saber, Cheng, Jingliang, Fu, Jiewen, Khan, Md Asaduzzaman, Fu, Junjiang. 2019. Novel splicing variant c. 208+2T>C in BBS5 segregates with Bardet-Biedl syndrome in an Iranian family by targeted exome sequencing. In Bioscience reports, 39, . doi:10.1042/BSR20181544. https://pubmed.ncbi.nlm.nih.gov/30850397/