2018
PLoS One. 2018 Apr 12;13(4):e0195747. doi: 10.1371/journal.pone.0195747. eCollection 2018.
UXT is required for spermatogenesis in mice.
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, United States of America. Pathobiology and Translational Medicine Training Program, New York University School of Medicine, New York, NY, United States of America. Department of Urology, New York University School of Medicine, New York, NY, United States of America. Department of Microbiology, New York University School of Medicine, New York, NY, United States of America. Institute for Systems Genetics, New York University Langone Medical Center, New York, New York, United States of America. Center for Health Informatics and Bioinformatics, New York University School of Medicine, New York, NY, United States of America. Department of Biology, Stern College, Yeshiva University, New York, NY, United States of America. Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, United States of America.
Service type: Knockout mice
Abstract
Male mammals must simultaneously produce prodigious numbers of sperm and maintain an adequate reserve of stem cells to ensure continuous production of gametes throughout life. Failures in the mechanisms responsible for balancing germ cell differentiation and spermatogonial stem cell (SSC) self-renewal can result in infertility. We discovered a novel requirement for Ubiquitous Expressed Transcript (UXT) in spermatogenesis by developing the first knockout mouse model for this gene. Constitutive deletion of Uxt is embryonic lethal, while conditional knockout in the male germline results in a Sertoli cell-only phenotype during the first wave of spermatogenesis that does not recover in the adult. This phenotype begins to manifest between 6 and 7 days post-partum, just before meiotic entry. Gene expression analysis revealed that Uxt deletion downregulates the transcription of genes governing SSC self-renewal, differentiation, and meiosis, consistent with its previously defined role as a transcriptional co-factor. Our study has revealed the first in vivo function for UXT in the mammalian germline as a regulator of distinct transcriptional programs in SSCs and differentiating spermatogonia.
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