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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.<\/jats:p>","DOI":"10.1242\/jcs.173666","type":"journal-article","created":{"date-parts":[[2015,12,12]],"date-time":"2015-12-12T03:08:37Z","timestamp":1449889717000},"page":"492-501","source":"Crossref","is-referenced-by-count":20,"title":["Germline deletion of huntingtin causes male infertility and arrested spermiogenesis in mice"],"prefix":"10.1242","volume":"129","author":[{"given":"Jinting","family":"Yan","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences 1 , Beijing 100101 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences 1 , Beijing 100101 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences 1 , Beijing 100101 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feilong","family":"Zhao","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences 1 , Beijing 100101 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences 2 , Beijing 100101 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengmei","family":"Xie","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences 1 , Beijing 100101 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tie-Shan","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences 2 , Beijing 100101 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixia","family":"Guo","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences 1 , Beijing 100101 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2024061316032749700_JCS173666C1","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/978-1-60761-103-5_16","article-title":"Staging of mouse seminiferous tubule cross-sections","volume":"558","author":"Ahmed","year":"2009","journal-title":"Methods Mol. 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