title: Germline deletion of huntingtin causes male infertility and arrested spermiogenesis in mice.
abstract: Human Huntingtin (HTT), a Huntington's disease gene, is highly expressed in the mammalian brain and testis. Simultaneous knockout of mouse Huntingtin (Htt) in brain and testis impairs male fertility, providing evidence for a link between Htt and spermatogenesis; however, the underlying mechanism remains unclear. To understand better the function of Htt in spermatogenesis, we restricted the genetic deletion specifically to the germ cells using the Cre/loxP site-specific recombination strategy and found that the resulting mice manifested smaller testes, azoospermia and complete male infertility. Meiotic chromosome spread experiments showed that the process of meiosis was normal in the absence of Htt. Notably, we found that Htt-deficient round spermatids did not progress beyond step 3 during the post-meiotic phase, when round spermatids differentiate into mature spermatozoa. Using an iTRAQ-based quantitative proteomic assay, we found that knockout of Htt significantly altered the testis protein profile. The differentially expressed proteins exhibited a remarkable enrichment for proteins involved in translation regulation and DNA packaging, suggesting that Htt might play a role in spermatogenesis by regulating translation and DNA packaging in the testis.
authors.affiliation: CAS Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jinting
authors.initials: J
authors.lastname: Yan
authors.affiliation: CAS Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Feilong
authors.initials: F
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhu
authors.affiliation: CAS Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Chengmei
authors.initials: C
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China guocx@big.ac.cn tangtsh@ioz.ac.cn.
authors.forename: Tie-Shan
authors.initials: TS
authors.lastname: Tang
authors.affiliation: CAS Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China guocx@big.ac.cn tangtsh@ioz.ac.cn.
authors.forename: Caixia
authors.initials: C
authors.lastname: Guo
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics*; D007248:Infertility, Male / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D040901:Proteomics / Q000379:methods; D017384:Sequence Deletion / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013087:Spermatids / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000378:metabolism
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D004247:DNA
keywords: DNA packaging; Huntingtin; Spermatogenesis; Spermiogenesis; Translation