Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella
Copyright policy )Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella
AbstractAberrant sperm flagella impair sperm motility and cause male infertility, yet the genes which have been identified in multiple morphological abnormalities of the flagella (MMAF) can only explain the pathogenic mechanisms of MMAF in a small number of cases. Here, we identify and functionally characterize homozygous loss-of-function mutations of QRICH2 in two infertile males with MMAF from two consanguineous families. Remarkably, Qrich2 knock-out (KO) male mice constructed by CRISPR-Cas9 technology present MMAF phenotypes and sterility. To elucidate the mechanisms of Qrich2 functioning in sperm flagellar formation, we perform proteomic analysis on the testes of KO and wild-type mice. Furthermore, in vitro experiments indicate that QRICH2 is involved in sperm flagellar development through stabilizing and enhancing the expression of proteins related to flagellar development. Our findings strongly suggest that the genetic mutations of human QRICH2 can lead to male infertility with MMAF and that QRICH2 is essential for sperm flagellar formation.
- Chinese Academy of Sciences (中国科学院) China (People's Republic of)
- Chinese Academy of Sciences China (People's Republic of)
- Chinese Academy of Science (中国科学院) China (People's Republic of)
- West China Second University Hospital of Sichuan University China (People's Republic of)
- Fudan University China (People's Republic of)
Adult, Male, Mice, Knockout, Science, Gene Expression Profiling, Q, Calcium-Binding Proteins, A Kinase Anchor Proteins, Gene Expression, Phosphoproteins, Article, Pedigree, Consanguinity, Mice, Loss of Function Mutation, Sperm Tail, Testis, Microtubule Proteins, Sperm Motility, Animals, Humans, Heat-Shock Proteins, Infertility, Male
Adult, Male, Mice, Knockout, Science, Gene Expression Profiling, Q, Calcium-Binding Proteins, A Kinase Anchor Proteins, Gene Expression, Phosphoproteins, Article, Pedigree, Consanguinity, Mice, Loss of Function Mutation, Sperm Tail, Testis, Microtubule Proteins, Sperm Motility, Animals, Humans, Heat-Shock Proteins, Infertility, Male
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