Cep135-flox Mouse

CEP135, also known as Bld10p in Chlamydomonas reinhardtii, is a conserved centriolar protein. It is essential for constructing the centriole and plays a central role in determining the number of triplets in the centriole independently of the cartwheel [2]. CEP135 is associated with the centrosome, which is the cell's central microtubule-organizing center, and is involved in various cellular processes like the cell cycle, angiogenesis, and cell migration [3].

In breast cancer cells, dysregulation of CEP135 isoforms (CEP135full and CEP135mini) promotes centriole overduplication and contributes to chromosome segregation errors. An increased CEP135full:mini ratio is observed in breast cancer cell lines with high centrosome amplification (CA). Inducing CEP135full expression increases CA, multipolar spindles, anaphase-lagging chromosomes, and micronuclei, while CEP135mini expression reduces centrosome number [1]. In mice, loss of Cep135 in premeiotic germ cells causes oligoasthenoteratozoospermia and male infertility. It leads to abnormal sperm morphology, germ cell apoptosis, and defects in acrosome, flagellum, and head-to-tail connections during spermatogenesis [4].

In conclusion, CEP135 is crucial for centriole structure and function, and its dysregulation is associated with breast cancer and male infertility. The gene knockout mouse models have been instrumental in uncovering its role in spermatogenesis, while studies in cancer cells have shown its importance in maintaining genomic stability, providing insights into disease mechanisms and potential therapeutic targets.