ArticleScience China. Life sciences2024
Gene-knockout by iSTOP enables rapid reproductive disease modeling and phenotyping in germ cells of the founder generation.
Article in Science China. Life sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
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- Deficiency of primate-specific TFDP3 causes male infertility with oligoasthenoteratozoospermia in humans and cynomolgus monkeys.Science China. Life sciences · 2026Article
- Stem cell-based embryo models: a tool to study early human development.Science China. Life sciences · 2025Review
- Function of manchette and intra-manchette transport in spermatogenesis and male fertility.Cell communication and signaling : CCS · 2025Review
- Generation of transient totipotent blastomere-like stem cells by short-term high-dose Pladienolide B treatment.Science China. Life sciences · 2025Article
- Efficient generation of all ESC-derived mice carrying a homozygous lethal mutation through eight-cell embryo injection.Science China. Life sciences · 2025Article
- Homozygous deleterious variants in MYCBPAP induce asthenoteratozoospermia involving abnormal acrosome biogenesis, manchette structure and sperm tail assembly in humans and mice.Science China. Life sciences · 2025Article
- MGA loss-of-function variants cause premature ovarian insufficiency.The Journal of clinical investigation · 2024Article
- Review
- Loss of Tet hydroxymethylase activity causes mouse embryonic stem cell differentiation bias and developmental defects.Science China. Life sciences · 2024Article
- Bi-allelic variants inHuman reproduction open · 2024Article
- Dnali1 is required for sperm motility and male fertility in mice.Basic and clinical andrology · 2023Article
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytosine base editing achieves C•G-to-T•A substitutions and can convert four codons (CAA/CAG/CGA/TGG) into STOP-codons (induction of STOP-codons, iSTOP) to knock out genes with reduced mosaicism. iSTOP enables direct phenotyping in founders' somatic cells, but it remains unknown whether this works in founders' germ cells so as to rapidly reveal novel genes for fertility. Here, we initially establish that iSTOP in mouse zygotes enables functional characterization of known genes in founders' germ cells: Cfap43-iSTOP male founders manifest expected sperm features resembling human "multiple morphological abnormalities of the flagella" syndrome (i.e., MMAF-like features), while oocytes of Zp3-iSTOP female founders have no zona pellucida. We further illustrate iSTOP's utility for dissecting the functions of unknown genes with Ccdc183, observing MMAF-like features and male infertility in Ccdc183-iSTOP founders, phenotypes concordant with those of Ccdc183-KO offspring. We ultimately establish that CCDC183 is essential for sperm morphogenesis through regulating the assembly of outer dynein arms and participating in the intra-flagellar transport. Our study demonstrates iSTOP as an efficient tool for direct reproductive disease modeling and phenotyping in germ cells of the founder generation, and rapidly reveals the essentiality of Ccdc183 in fertility, thus providing a time-saving approach for validating genetic defects (like nonsense mutations) for human infertility.
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