TY - JOUR TI - Absence of CEP78 causes photoreceptor and sperm flagella impairments in mice and a human individual AU - Zhu, Tianyu AU - Zhang, Yuxin AU - Sheng, Xunlun AU - Zhang, Xiangzheng AU - Chen, Yu AU - Zhu, Hongjing AU - Guo, Yueshuai AU - Qi, Yaling AU - Zhao, Yichen AU - Zhou, Qi AU - Chen, Xue AU - Guo, Xuejiang AU - Zhao, Chen A2 - Pedersen, Lotte B A2 - Azziz, Ricardo VL - 12 PY - 2023 DA - 2023/02/09 SP - e76157 C1 - eLife 2023;12:e76157 DO - 10.7554/eLife.76157 UR - https://doi.org/10.7554/eLife.76157 AB - Cone-rod dystrophy (CRD) is a genetically inherited retinal disease that can be associated with male infertility, while the specific genetic mechanisms are not well known. Here, we report CEP78 as a causative gene of a particular syndrome including CRD and male infertility with multiple morphological abnormalities of sperm flagella (MMAF) both in human and mouse. Cep78 knockout mice exhibited impaired function and morphology of photoreceptors, typified by reduced ERG amplitudes, disrupted translocation of cone arrestin, attenuated and disorganized photoreceptor outer segments (OS) disks and widen OS bases, as well as interrupted connecting cilia elongation and abnormal structures. Cep78 deletion also caused male infertility and MMAF, with disordered ‘9+2’ structure and triplet microtubules in sperm flagella. Intraflagellar transport (IFT) proteins IFT20 and TTC21A are identified as interacting proteins of CEP78. Furthermore, CEP78 regulated the interaction, stability, and centriolar localization of its interacting protein. Insufficiency of CEP78 or its interacting protein causes abnormal centriole elongation and cilia shortening. Absence of CEP78 protein in human caused similar phenotypes in vision and MMAF as Cep78−/− mice. Collectively, our study supports the important roles of CEP78 defects in centriole and ciliary dysfunctions and molecular pathogenesis of such multi-system syndrome. KW - CEP78 KW - male infertility KW - cone-rod dystrophy KW - IFT20 KW - TTC21A JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -