Cep250-KO Mouse

CEP250, encoding the C-Nap1 protein, belongs to the CEP protein family. It serves as a docking protein for fibers linking centrioles, playing a crucial role in maintaining centrosome cohesion, which is essential for cell divisions in processes like male gametogenesis. It may also be involved in pathways related to ciliopathy-associated retinal degeneration, as photoreceptor cilium is affected in Cep250-related disorders [1,4]. Genetic models, especially mouse models, have been valuable in studying its function.

In male mice, knockout of Cep250 leads to male infertility due to a reduction in the spermatogonial pool and meiotic blockade, with centrosomes splitting up precociously in differentiating spermatogonia and meiotic spermatocytes [1]. In mice, homozygous knockout of Cep250 causes a relatively late-onset retinal degeneration and sensorineural hearing loss. Retinal function gradually declines with age, and histological analysis confirms the late-onset retinal degeneration [2]. A novel nonsense variant in CEP250 in humans leads to protein mislocalization, centrosome localization deficit, hair cell degeneration in the cochlea, and progressive hearing loss, and similar phenotypes are seen in knockout mice [3]. Dysregulated arginine metabolism contributes to retinal degeneration in Cep250 knockout mice, and RNA-seq analysis shows dysregulation of cGMP-PKG-MAPK pathways in these mice, which may be related to the pathogenesis of cilia-related retinal degeneration [4,5].

In conclusion, Cep250 is essential for maintaining centrosome cohesion, especially in male germ cells, and is also crucial for normal retinal and cochlear function. The study of Cep250 knockout mouse models has provided significant insights into the mechanisms of male infertility, retinal degeneration, and sensorineural hearing loss, highlighting its importance in these disease areas.

References:

1. Floriot, Sandrine, Bellutti, Laura, Castille, Johan, Vilotte, Jean-Luc, Livera, Gabriel. 2022. CEP250 is Required for Maintaining Centrosome Cohesion in the Germline and Fertility in Male Mice. In Frontiers in cell and developmental biology, 9, 754054. doi:10.3389/fcell.2021.754054. https://pubmed.ncbi.nlm.nih.gov/35127699/

2. Abu-Diab, Alaa, Gopalakrishnan, Prakadeeswari, Matsevich, Chen, Sharon, Dror, Khateb, Samer. . Homozygous Knockout of Cep250 Leads to a Relatively Late-Onset Retinal Degeneration and Sensorineural Hearing Loss in Mice. In Translational vision science & technology, 12, 3. doi:10.1167/tvst.12.3.3. https://pubmed.ncbi.nlm.nih.gov/36857066/

3. Kang, Minjin, Kim, Jung Ah, Song, Mee Hyun, Gee, Heon Yung, Jung, Jinsei. 2023. Novel Variant in CEP250 Causes Protein Mislocalization and Leads to Nonsyndromic Autosomal Recessive Type of Progressive Hearing Loss. In Cells, 12, . doi:10.3390/cells12182328. https://pubmed.ncbi.nlm.nih.gov/37759551/

4. Xiang, Lue, Yang, Qiao-Li, Xie, Bin-Tao, Chen, Qi, Huang, Xiu-Feng. . Dysregulated Arginine Metabolism Is Linked to Retinal Degeneration in Cep250 Knockout Mice. In Investigative ophthalmology & visual science, 64, 2. doi:10.1167/iovs.64.12.2. https://pubmed.ncbi.nlm.nih.gov/37656476/

5. Chen, Chong, Rong, Yu, Zhuang, Youyuan, Qu, Jia, Liu, Xinting. 2023. RNA-Seq Analysis Reveals an Essential Role of the cGMP-PKG-MAPK Pathways in Retinal Degeneration Caused by Cep250 Deficiency. In International journal of molecular sciences, 24, . doi:10.3390/ijms24108843. https://pubmed.ncbi.nlm.nih.gov/37240188/