气候变化领域集成服务门户(CCPortal): Knockout of the HMG domain of the porcine SRY gene causes sex reversal in gene-edited pigs

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DOI	10.1073/pnas.2008743118
	Knockout of the HMG domain of the porcine SRY gene causes sex reversal in gene-edited pigs
	Kurtz S.; Lucas-Hahn A.; Schlegelberger B.; Göhring G.; Niemann H.; Mettenleiter T.C.; Petersen B.
发表日期	2021
ISSN	00278424
卷号	118 期号:2
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CRISPR/Cas9; HMG domain; Porcine SRY gene; RNPs; Sex reversal
语种	英语
scopus关键词	CRISPR associated endonuclease Cas9; CRISPR associated protein; forkhead box protein L2; gonadotropin; high mobility group protein; 5' flanking region; animal cell; animal experiment; animal tissue; Article; chromosome 7; controlled study; female; female genital system; frameshift mutation; gene duplication; gene editing; gene expression; gene locus; gene sequence; genotype; immunohistochemistry; male; male genital system; nonhuman; phenotype; piglet; polymerase chain reaction; priority journal; sex determination; sex transformation; SRY gene
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181094
作者单位	Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Mariensee, Neustadt am Rübenberge, 31535, Germany; Institute of Human Genetics, Hannover Medical School, Hannover, 30625, Germany; Clinic for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, 30625, Germany; Friedrich-Loeffler-Institut, 17493 Greifswald, Insel Riems, Germany
推荐引用方式 GB/T 7714	Kurtz S.,Lucas-Hahn A.,Schlegelberger B.,et al. Knockout of the HMG domain of the porcine SRY gene causes sex reversal in gene-edited pigs[J],2021,118(2).
APA	Kurtz S..,Lucas-Hahn A..,Schlegelberger B..,Göhring G..,Niemann H..,...&Petersen B..(2021).Knockout of the HMG domain of the porcine SRY gene causes sex reversal in gene-edited pigs.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA	Kurtz S.,et al."Knockout of the HMG domain of the porcine SRY gene causes sex reversal in gene-edited pigs".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).