Wdr7-KO Mouse

Wdr7, short for WD repeat domain 7, is involved in multiple biological processes. It is part of the rabconnectin3 (Rbcn3) complex, which is associated with V-ATPase, contributing to pH regulation in secretory and endocytic pathways. It may also be associated with cell apoptosis, cell cycle [4], and is potentially involved in signaling pathways like WDR7-7-GPR30 [6,7].

Recent studies have identified Wdr7 as a gene associated with amyotrophic lateral sclerosis (ALS) [1,5]. Genome-wide CRISPR screenings have shown that Wdr7 is an essential host factor for the replication of influenza A virus [2], Rift Valley fever phlebovirus (RVFV), and La Crosse encephalitis virus (LACV) [3,8]. Silencing Wdr7 significantly impaired RVFV replication, with its knockout affecting RVFV replication at a later phase of its cycle [3,8]. In breast cancer research, knocking down the neighboring non-coding RNA lincRNA-RoR led to an up-regulation of Wdr7 [4]. Also, calycosin inhibited breast cancer cell proliferation through the WDR7-7-GPR30 signaling pathway [7].

In summary, Wdr7 plays crucial roles in various biological processes and disease conditions. Its functions range from being a host factor for virus replication to being potentially involved in neurological disorders like ALS and in breast cancer cell proliferation. The gene knockout and knockdown studies have been instrumental in revealing these functions, offering insights into potential therapeutic targets for related diseases.

References:

1. Wang, Hui, Guan, LiPing, Deng, Min. 2023. Recent progress of the genetics of amyotrophic lateral sclerosis and challenges of gene therapy. In Frontiers in neuroscience, 17, 1170996. doi:10.3389/fnins.2023.1170996. https://pubmed.ncbi.nlm.nih.gov/37250416/

2. Li, Bo, Clohisey, Sara M, Chia, Bing Shao, Baillie, J Kenneth, Hacohen, Nir. 2020. Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection. In Nature communications, 11, 164. doi:10.1038/s41467-019-13965-x. https://pubmed.ncbi.nlm.nih.gov/31919360/

3. Balaraman, Velmurugan, Indran, Sabarish V, Li, Yonghai, Weber, Friedemann, Richt, Juergen A. 2023. Identification of Host Factors for Rift Valley Fever Phlebovirus. In Viruses, 15, . doi:10.3390/v15112251. https://pubmed.ncbi.nlm.nih.gov/38005928/

4. Kor, Sara, Erfani-Moghadam, Vahid, Sahebi, Reza, Bahramian, Shabbou, Shafiee, Mohammad. . WDR7 up-regulation upon knocking down of neighboring non-coding RNA using siRNAs encapsulated in polyamidoamine dendrimers. In Iranian journal of basic medical sciences, 22, 1283-1287. doi:10.22038/ijbms.2019.36135.8607. https://pubmed.ncbi.nlm.nih.gov/32128092/

5. Brenner, David, Freischmidt, Axel. 2022. Update on genetics of amyotrophic lateral sclerosis. In Current opinion in neurology, 35, 672-677. doi:10.1097/WCO.0000000000001093. https://pubmed.ncbi.nlm.nih.gov/35942673/

6. Deng, Mao, Chen, Huijuan, Long, Jiaying, Xie, Long, Li, Xiaofang. 2020. Calycosin: a Review of its Pharmacological Effects and Application Prospects. In Expert review of anti-infective therapy, 19, 911-925. doi:10.1080/14787210.2021.1863145. https://pubmed.ncbi.nlm.nih.gov/33346681/

7. Tian, Jing, Wang, Yong, Zhang, Xing, Lu, Huiling, Chen, Jian. 2017. Calycosin inhibits the in vitro and in vivo growth of breast cancer cells through WDR7-7-GPR30 Signaling. In Journal of experimental & clinical cancer research : CR, 36, 153. doi:10.1186/s13046-017-0625-y. https://pubmed.ncbi.nlm.nih.gov/29096683/

8. Balaraman, Velmurugan, Indran, Sabarish V, Li, Yonghai, Weber, Friedemann, Richt, Juergen A. 2023. Identification of host factors for Rift Valley Fever Phlebovirus. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.09.28.559935. https://pubmed.ncbi.nlm.nih.gov/37808812/