ArticleProceedings of the National Academy of Sciences of the United States of America2021
Knockout of the HMG domain of the porcine SRY gene causes sex reversal in gene-edited pigs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Horizon scanning of potential environmental applications of terrestrial animals, fish, algae and microorganisms produced by genetic modification, including the use of new genomic techniques.Frontiers in genome editing · 2024Pooled it
- Female- or male-biased offspring generated by targeted distortion of sex chromosome transmission in the mouse.Genetics · 2026Article
- Sex and the Developmental Environment Shape Molecular Networks Underlying Bronchial Responsiveness in Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- CRISPR/Cas9-mediated TOP1 knockout in chicken DF-1 cells reveals its critical role in apoptosis regulation and genomic stability.Journal of animal science · 2026Article
- Current and future uses of genetic improvement technologies in livestock breeding programs.Animal frontiers : the review magazine of animal agriculture · 2025Article
- Deciphering the Role of theInternational journal of molecular sciences · 2024Article
- First sex modification case in equine cloning.PloS one · 2023Article
- Quantitative analysis of CRISPR/Cas9-mediated provirus deletion in blue egg layer chicken PGCs by digital PCR.Scientific reports · 2022Article
- Early Gonadal Development and Sex Determination in Mammal.International journal of molecular sciences · 2022Review
- In vitro genome editing activity of Cas9 in somatic cells after random and transposon-based genomic Cas9 integration.PloS one · 2022Article
- Adenine base-editing-mediated exon skipping induces gene knockout in cultured pig cells.Biotechnology letters · 2022Article
- Advances in CRISPR-Based Functional Genomics and Nucleic Acid Detection in Pigs.Frontiers in genetics · 2022Article
- CRISPR/Cas9-editing ofFrontiers in genetics · 2022Article
- Alternate Roles of Sox Transcription Factors beyond Transcription Initiation.International journal of molecular sciences · 2021Review
- Perspectives for Buck Kids in Dairy Goat Farming.Frontiers in veterinary science · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The sex-determining region on the Y chromosome (SRY) is thought to be the central genetic element of male sex development in mammals. Pathogenic modifications within the SRY gene are associated with a male-to-female sex reversal syndrome in humans and other mammalian species, including rabbits and mice. However, the underlying mechanisms are largely unknown. To understand the biological function of the SRY gene, a site-directed mutational analysis is required to investigate associated phenotypic changes at the molecular, cellular, and morphological level. Here, we successfully generated a knockout of the porcine SRY gene by microinjection of two CRISPR-Cas ribonucleoproteins, targeting the centrally located "high mobility group" (HMG), followed by a frameshift mutation of the downstream SRY sequence. This resulted in the development of genetically male (XY) pigs with complete external and internal female genitalia, which, however, were significantly smaller than in 9-mo-old age-matched control females. Quantitative digital PCR analysis revealed a duplication of the SRY locus in Landrace pigs similar to the known palindromic duplication in Duroc breeds. Our study demonstrates the central role of the HMG domain in the SRY gene in male porcine sex determination. This proof-of-principle study could assist in solving the problem of sex preference in agriculture to improve animal welfare. Moreover, it establishes a large animal model that is more comparable to humans with regard to genetics, physiology, and anatomy, which is pivotal for longitudinal studies to unravel mammalian sex determination and relevant for the development of new interventions for human sex development disorders.
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