{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nDCAF17 is a substrate receptor for the Cullin‐RING E3 ubiquitin ligase complex, playing a pivotal role in testicular development and spermatogenesis. Expression studies in wild‐type mice reveal that Dcaf17 is highly expressed in the testis with transcript levels increasing progressively during post‐natal development. Disruption of Dcaf17 leads to severe defects in spermiogenesis—including abnormal acrosome capping, impaired nuclear compaction, and abnormal transition from round to elongated spermatids—resulting in reduced sperm number, aberrant morphology, decreased motility, and consequent male infertility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn humans, loss‐of-function variants in DCAF17 are associated with a complex syndrome that includes features such as hypergonadotropic hypogonadism, partial alopecia, diabetes mellitus, and cognitive deficits, highlighting its critical role in gonadal development. A study of affected individuals, together with a CRISPR/Cas9-generated mouse model mimicking the disruption, confirmed that Dcaf17 dysfunction results in compromised fertility—with male infertility and female subfertility—thereby underscoring its fundamental contributions to reproductive biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther investigation using RNA-sequencing of testes from Dcaf17-disrupted mice revealed widespread transcriptional perturbations. Notably, genes involved in proteolysis, transcription regulation, and chromatin remodeling were significantly altered, with an up-regulation of somatic and early spermatogenic markers and a down-regulation of those normally enriched in later-stage round spermatids. These molecular alterations likely impair testicular proteostasis and contribute to the aberrant development of germ cells, thereby providing insights into the mechanisms underlying Dcaf17-mediated infertility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Asmaa Ali, Bhavesh V Mistry, Hala A Ahmed, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletion of DDB1- and CUL4- associated factor-17 (Dcaf17) gene causes spermatogenesis defects and male infertility in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-27379-0"}], "href": "https://doi.org/10.1038/s41598-018-27379-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29907856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29907856"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "F Gurbuz, S Desai, F Diao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel inactivating mutations of the DCAF17 gene in American and Turkish families cause male infertility and female subfertility in the mouse model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.13183"}], "href": "https://doi.org/10.1111/cge.13183"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29178422"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29178422"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Raed Abu-Dawud, Bhavesh V Mistry, Mohamed Rajab, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of male fertility-critical Dcaf17 dysregulates mouse testis transcriptome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-022-25826-7"}], "href": "https://doi.org/10.1038/s41598-022-25826-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36509865"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36509865"}]}]}]}