Iqcg Is Essential for Sperm Flagellum Formation in Mice
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{"title"=>"Iqcg is essential for sperm flagellum formation in mice", "type"=>"journal", "authors"=>[{"first_name"=>"Ren Ke", "last_name"=>"Li", "scopus_author_id"=>"26643151100"}, {"first_name"=>"Jue Ling", "last_name"=>"Tan", "scopus_author_id"=>"56150852100"}, {"first_name"=>"Li Ting", "last_name"=>"Chen", "scopus_author_id"=>"56151247300"}, {"first_name"=>"Jing Sheng", "last_name"=>"Feng", "scopus_author_id"=>"23472814600"}, {"first_name"=>"Wen Xue", "last_name"=>"Liang", "scopus_author_id"=>"57198709394"}, {"first_name"=>"Xue Jiang", "last_name"=>"Guo", "scopus_author_id"=>"20734064800"}, {"first_name"=>"Ping", "last_name"=>"Liu", "scopus_author_id"=>"56883437700"}, {"first_name"=>"Zhu", "last_name"=>"Chen", "scopus_author_id"=>"57075281300"}, {"first_name"=>"Jia Hao", "last_name"=>"Sha", "scopus_author_id"=>"7102192441"}, {"first_name"=>"Yi Fei", "last_name"=>"Wang", "scopus_author_id"=>"57200052113"}, {"first_name"=>"Sai Juan", "last_name"=>"Chen", "scopus_author_id"=>"13302986900"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"24849454", "doi"=>"10.1371/journal.pone.0098053", "pui"=>"373161048", "issn"=>"19326203", "sgr"=>"84901325120", "scopus"=>"2-s2.0-84901325120"}, "id"=>"35ed4422-9ac4-3fc1-9f5e-ec58c855f59a", "abstract"=>"Mammalian spermatogenesis comprises three successive phases: mitosis phase, meiosis phase, and spermiogenesis. During spermiogenesis, round spermatid undergoes dramatic morphogenesis to give rise to mature spermatozoon, including the condensation and elongation of nucleus, development of acrosome, formation of flagellum, and removal of excessive cytoplasm. Although these transformations are well defined at the morphological level, the mechanisms underlying these intricate processes are largely unknown. Here, we report that Iqcg, which was previously characterized to be involved in a chromosome translocation of human leukemia, is highly expressed in the spermatogenesis of mice and localized to the manchette in developing spermatids. Iqcg knockout causes male infertility, due to severe defects of spermiogenesis and resultant total immobility of spermatozoa. The axoneme in the Iqcg knockout sperm flagellum is disorganized and hardly any typical (‘‘9+2’’) pattern of microtubule arrangement could be found in Iqcg knockout spermatids. Iqcg interacts with calmodulin in a calcium dependent manner in the testis, suggesting that Iqcg may play a role through calcium signaling. Furthermore, cilia structures in the trachea and oviduct, as well as histological appearances of other major tissues, remain unchanged in the Iqcg knockout mice, suggesting that Iqcg is specifically required for spermiogenesis in mammals. These results might also provide new insights into the genetic causes of human infertility", "link"=>"http://www.mendeley.com/research/iqcg-essential-sperm-flagellum-formation-mice", "reader_count"=>11, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>7, "Psychology"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Social Sciences"=>{"Social Sciences"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1505993"], "description"=>"<p>(A) <i>Iqcg</i> mRNA levels in different tissues analyzed by quantitative RT-PCR using total RNA extracted from different tissues of mice. BM: bone marrow. Products of reverse transcription reaction with no mRNA templates were used as negative control (NC). Experiments were performed in triplicate and data were presented as means ± SEM. (B) Expression of Iqcg protein in different tissues. Gapdh was used as a loading control. (C) <i>Iqcg</i> mRNA levels in the first wave of spermatogenesis of mice. (D) X-gal staining of WT and <i>Iqcg</i> HE (heterozygote) testis sections. The X-gal reaction product (blue stain) was abundant in the spermatocytes and spermatids. Nucleus was counterstained with nuclear fast red. Scale bar  = 50 µm. (E) Immunohistochemical analysis of Iqcg protein in the WT testis sections. In stage V section, Iqcg was observed in the spermatids but not in spermatogonia or spermatocytes. Iqcg began to appear in the pachytene spermatocytes at stage VI. This signal persisted and was finally localized to the flagella of mature spermatozoa of testis, which can be seen in the lumens of testis sections at stage VI and stage VIII. Stage XI section showed Iqcg expression in diplotene spermatocytes but not in zygotene spermatocytes. The stages of seminiferous epithelial cycle were denoted by the Roman numerals. Different cell types of spermatocytes were indicated by the arrows. P: pachytene spermatocyte; Z: zygotene spermatocyte; D: diplotene spermatocyte; R: round spermatid. Scale bar  = 20 µm. (F) Immunofluorescence analysis of Iqcg on the slides of epididymal sperm. Iqcg was localized in the flagellum and post acrosomal region of sperm head. DAPI was used to stain nucleus. Scale bar  = 10 µm. (G) Western blot analysis of the sperm fractions after SDS-EDTA treatment. Iqcg was retained in the soluble fraction after this treatment. β-tubulin and Odf1 were used as controls for the soluble (Sup.) and SDS-resistant (Pellet) fractions respectively.</p>", "links"=>[], "tags"=>["biophysics", "cell biology", "Cell motility", "Ciliary movement", "Flagellar motility", "Cellular structures and organelles", "cytoskeleton", "microtubules", "Molecular cell biology", "developmental biology", "Cell differentiation", "urology", "infertility", "orderly", "spermatogenesis"], "article_id"=>1033211, "categories"=>["Biological Sciences"], "users"=>["Ren-Ke Li", "Jue-Ling Tan", "Li-Ting Chen", "Jing-Sheng Feng", "Wen-Xue Liang", "Xue-Jiang Guo", "Ping Liu", "Zhu Chen", "Jia-Hao Sha", "Yi-Fei Wang", "Sai-Juan Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0098053.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Iqcg_was_highly_and_orderly_expressed_in_spermatogenesis_of_mice_/1033211", "title"=>"<i>Iqcg</i> was highly and orderly expressed in spermatogenesis of mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-21 03:18:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1505994"], "description"=>"<p>Immunofluorescence was performed on the drying down preparations corresponding with spermatids of different steps. α-tubulin was used as a marker for manchette. DAPI was used to stain nucleus. Scale bar  = 20 µm.</p>", "links"=>[], "tags"=>["biophysics", "cell biology", "Cell motility", "Ciliary movement", "Flagellar motility", "Cellular structures and organelles", "cytoskeleton", "microtubules", "Molecular cell biology", "developmental biology", "Cell differentiation", "urology", "infertility", "manchette"], "article_id"=>1033212, "categories"=>["Biological Sciences"], "users"=>["Ren-Ke Li", "Jue-Ling Tan", "Li-Ting Chen", "Jing-Sheng Feng", "Wen-Xue Liang", "Xue-Jiang Guo", "Ping Liu", "Zhu Chen", "Jia-Hao Sha", "Yi-Fei Wang", "Sai-Juan Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0098053.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Iqcg_was_associated_with_manchette_in_the_developing_spermatids_/1033212", "title"=>"Iqcg was associated with manchette in the developing spermatids.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-21 03:18:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1505995"], "description"=>"<p>(A) Schematic of the “knockout first” targeting strategy used for generating <i>Iqcg</i> KO mice. This strategy introduced an Flp-recombinase target (FRT)-flanked selection cassette into the intron after the fifth exon of <i>Iqcg</i>, which could trap the transcript through the Engrailed-2 splice acceptor (En2 sA) element and truncate it through the SV40 polyadenylation signal (pA). LacZ encoding β-galactosidase was a reporter gene that could be used to trace the expression pattern of the <i>Iqcg</i>. Neomycin resistance gene (Neo) was used as a marker for ES clone screening which was driven by an autonomous promoter (hBactP). IRES: internal ribosome entry site. (B) A representative genotyping by PCR assay using primers specific for mouse <i>Iqcg</i> (5′arm and 3′arm) and LAR3 (designed on the En2 SA element of the targeted allele). HE: heterozygote. (C) KO efficiency examined by Western blot analysis in representative tissues.</p>", "links"=>[], "tags"=>["biophysics", "cell biology", "Cell motility", "Ciliary movement", "Flagellar motility", "Cellular structures and organelles", "cytoskeleton", "microtubules", "Molecular cell biology", "developmental biology", "Cell differentiation", "urology", "infertility", "knockout"], "article_id"=>1033213, "categories"=>["Biological Sciences"], "users"=>["Ren-Ke Li", "Jue-Ling Tan", "Li-Ting Chen", "Jing-Sheng Feng", "Wen-Xue Liang", "Xue-Jiang Guo", "Ping Liu", "Zhu Chen", "Jia-Hao Sha", "Yi-Fei Wang", "Sai-Juan Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0098053.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Generation_of_Iqcg_knockout_mice_/1033213", "title"=>"Generation of <i>Iqcg</i> knockout mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-21 03:18:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1506019"], "description"=>"<p>(A) H&E staining of WT and <i>Iqcg</i> KO testis and epididymis sections. In the WT testis, the lumens of seminiferous tubules of stage VII-VIII were filled with flagella. However, in the KO mice, no visible flagella could be found. The caput of WT epididymis displayed some spermatozoa in the lumens, but no spermatozoa were observed in the KO caput epididymis. WT cauda epididymis were filled with normal spermatozoa with long tails. However, the KO cauda epididymis only contained malformed spermatozoa and degenerated cell debris. The stages of seminiferous epithelial cycle were denoted by the Roman numerals. Scale bar  = 50 µm. (B) H&E staining of WT and <i>Iqcg</i> KO spermatozoa on slides. WT spermatozoa showed a thin and long flagellum (a). Most KO spermatozoa showed an extremely short tail and were often connected by a mass of cytoplasm (b). Some KO spermatozoa only showed a short tail (c). A part of KO spermatozoa also displayed nuclear shaping defects (d). Scale bar  = 20 µm.</p>", "links"=>[], "tags"=>["biophysics", "cell biology", "Cell motility", "Ciliary movement", "Flagellar motility", "Cellular structures and organelles", "cytoskeleton", "microtubules", "Molecular cell biology", "developmental biology", "Cell differentiation", "urology", "infertility", "sperm", "flagellum"], "article_id"=>1033215, "categories"=>["Biological Sciences"], "users"=>["Ren-Ke Li", "Jue-Ling Tan", "Li-Ting Chen", "Jing-Sheng Feng", "Wen-Xue Liang", "Xue-Jiang Guo", "Ping Liu", "Zhu Chen", "Jia-Hao Sha", "Yi-Fei Wang", "Sai-Juan Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0098053.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Iqcg_was_required_for_sperm_flagellum_formation_in_mice_/1033215", "title"=>"<i>Iqcg</i> was required for sperm flagellum formation in mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-21 03:18:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1506026"], "description"=>"<p>(A) WT epididymis sections showed different segments of sperm flagellum. (B) In <i>Iqcg</i> KO epididymis, no normal flagellum structures were found. The sperm head was often associated with a mass of cytoplasm where components of flagellum were found but could not be assembled correctly. (C) WT section of testis at stage VIII, which displayed the well-organized structures of middle piece, principle piece and end piece of step 16 sperm flagellum. (D) <i>Iqcg</i> KO step16 spermatid, showing similar malformation as the epididymal sperm. (E) A cross section of two heads of step 11 spermatids showing the normal nuclear shape. (F) A step 12 KO spermatid showed malformed head shape. The cross section in the acrosome region of this spermatid displayed distorted shape of the nucleus and the acroplaxome. (G) WT step 11–12 spermatid, showing the well assembled manchette (indicated by arrows and “M”). (H) KO spermatid at step 11–12, showing normal manchette structure. (I) WT step 9 spermatid showed that the centriole had been located to the posterior region of the nucleus. (J) Centriole in KO step 9 spermatid also showed successful migration to posterior region of the nucleus. (K) Cross section of WT step 16 spermatid at middle piece, showing the regular arrangement of mitochondria, outer dense fibers and microtubules. (L) Cross section of KO step 16 spermatid at middle piece, showing mitochondria and outer dense fibers, but the inner “9+2” arrangement of microtubules were missing. Scale bar  = 1 µm.</p>", "links"=>[], "tags"=>["biophysics", "cell biology", "Cell motility", "Ciliary movement", "Flagellar motility", "Cellular structures and organelles", "cytoskeleton", "microtubules", "Molecular cell biology", "developmental biology", "Cell differentiation", "urology", "infertility", "knockout"], "article_id"=>1033218, "categories"=>["Biological Sciences"], "users"=>["Ren-Ke Li", "Jue-Ling Tan", "Li-Ting Chen", "Jing-Sheng Feng", "Wen-Xue Liang", "Xue-Jiang Guo", "Ping Liu", "Zhu Chen", "Jia-Hao Sha", "Yi-Fei Wang", "Sai-Juan Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0098053.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ultrastructural_analysis_of_Iqcg_knockout_spermiogenesis_/1033218", "title"=>"Ultrastructural analysis of <i>Iqcg</i> knockout spermiogenesis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-21 03:18:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1506027"], "description"=>"<p>(A) Co-immunoprecipitation was performed in the cell lysates from WT and <i>Iqcg</i> KO testis using Iqcg antibody. Western blot analyses were conducted with Iqcg and calmodulin antibody. (B) Both Iqcg (green) and calmodulin (red) existed in the manchette region of elongating spermatids. DAPI was used to stain nucleus. Scale bar  = 5 µm. (C) Iqcg (green) and calmodulin (red) localization in epididymal spermatozoa. Both Iqcg and calmodulin were found in the flagellum and post-acrosomal region. DAPI was used to stain nucleus. Scale bar  = 10 µm.</p>", "links"=>[], "tags"=>["biophysics", "cell biology", "Cell motility", "Ciliary movement", "Flagellar motility", "Cellular structures and organelles", "cytoskeleton", "microtubules", "Molecular cell biology", "developmental biology", "Cell differentiation", "urology", "infertility", "interacted", "calmodulin", "testis", "calcium", "regulated"], "article_id"=>1033219, "categories"=>["Biological Sciences"], "users"=>["Ren-Ke Li", "Jue-Ling Tan", "Li-Ting Chen", "Jing-Sheng Feng", "Wen-Xue Liang", "Xue-Jiang Guo", "Ping Liu", "Zhu Chen", "Jia-Hao Sha", "Yi-Fei Wang", "Sai-Juan Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0098053.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Iqcg_interacted_with_calmodulin_in_testis_in_a_calcium_concentration_regulated_manner_/1033219", "title"=>"Iqcg interacted with calmodulin in testis in a calcium concentration regulated manner.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-21 03:18:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1506028"], "description"=>"<p><i>Iqcg</i> knockout caused male infertility.</p>", "links"=>[], "tags"=>["biophysics", "cell biology", "Cell motility", "Ciliary movement", "Flagellar motility", "Cellular structures and organelles", "cytoskeleton", "microtubules", "Molecular cell biology", "developmental biology", "Cell differentiation", "urology", "infertility", "knockout", "caused"], "article_id"=>1033220, "categories"=>["Biological Sciences"], "users"=>["Ren-Ke Li", "Jue-Ling Tan", "Li-Ting Chen", "Jing-Sheng Feng", "Wen-Xue Liang", "Xue-Jiang Guo", "Ping Liu", "Zhu Chen", "Jia-Hao Sha", "Yi-Fei Wang", "Sai-Juan Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0098053.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Iqcg_knockout_caused_male_infertility_/1033220", "title"=>"<i>Iqcg</i> knockout caused male infertility.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-05-21 03:18:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1506088", "https://ndownloader.figshare.com/files/1506090", "https://ndownloader.figshare.com/files/1506091", "https://ndownloader.figshare.com/files/1506092", "https://ndownloader.figshare.com/files/1506093", "https://ndownloader.figshare.com/files/1506094", "https://ndownloader.figshare.com/files/1506095", "https://ndownloader.figshare.com/files/1506096", "https://ndownloader.figshare.com/files/1506097", "https://ndownloader.figshare.com/files/1506098", "https://ndownloader.figshare.com/files/1506099", "https://ndownloader.figshare.com/files/1506100", "https://ndownloader.figshare.com/files/1506101", "https://ndownloader.figshare.com/files/1506102", "https://ndownloader.figshare.com/files/1506103", "https://ndownloader.figshare.com/files/1506104"], "description"=>"<div><p>Mammalian spermatogenesis comprises three successive phases: mitosis phase, meiosis phase, and spermiogenesis. During spermiogenesis, round spermatid undergoes dramatic morphogenesis to give rise to mature spermatozoon, including the condensation and elongation of nucleus, development of acrosome, formation of flagellum, and removal of excessive cytoplasm. Although these transformations are well defined at the morphological level, the mechanisms underlying these intricate processes are largely unknown. Here, we report that <i>Iqcg</i>, which was previously characterized to be involved in a chromosome translocation of human leukemia, is highly expressed in the spermatogenesis of mice and localized to the manchette in developing spermatids. <i>Iqcg</i> knockout causes male infertility, due to severe defects of spermiogenesis and resultant total immobility of spermatozoa. The axoneme in the <i>Iqc</i>g knockout sperm flagellum is disorganized and hardly any typical (“9+2”) pattern of microtubule arrangement could be found in <i>Iqcg</i> knockout spermatids. Iqcg interacts with calmodulin in a calcium dependent manner in the testis, suggesting that Iqcg may play a role through calcium signaling. Furthermore, cilia structures in the trachea and oviduct, as well as histological appearances of other major tissues, remain unchanged in the <i>Iqcg</i> knockout mice, suggesting that <i>Iqcg</i> is specifically required for spermiogenesis in mammals. These results might also provide new insights into the genetic causes of human infertility.</p></div>", "links"=>[], "tags"=>["biophysics", "cell biology", "Cell motility", "Ciliary movement", "Flagellar motility", "Cellular structures and organelles", "cytoskeleton", "microtubules", "Molecular cell biology", "developmental biology", "Cell differentiation", "urology", "infertility", "sperm", "flagellum"], "article_id"=>1033272, "categories"=>["Biological Sciences"], "users"=>["Ren-Ke Li", "Jue-Ling Tan", "Li-Ting Chen", "Jing-Sheng Feng", "Wen-Xue Liang", "Xue-Jiang Guo", "Ping Liu", "Zhu Chen", "Jia-Hao Sha", "Yi-Fei Wang", "Sai-Juan Chen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0098053.s001", "https://dx.doi.org/10.1371/journal.pone.0098053.s002", "https://dx.doi.org/10.1371/journal.pone.0098053.s003", "https://dx.doi.org/10.1371/journal.pone.0098053.s004", "https://dx.doi.org/10.1371/journal.pone.0098053.s005", "https://dx.doi.org/10.1371/journal.pone.0098053.s006", "https://dx.doi.org/10.1371/journal.pone.0098053.s007", "https://dx.doi.org/10.1371/journal.pone.0098053.s008", "https://dx.doi.org/10.1371/journal.pone.0098053.s009", "https://dx.doi.org/10.1371/journal.pone.0098053.s010", "https://dx.doi.org/10.1371/journal.pone.0098053.s011", "https://dx.doi.org/10.1371/journal.pone.0098053.s012", "https://dx.doi.org/10.1371/journal.pone.0098053.s013", "https://dx.doi.org/10.1371/journal.pone.0098053.s014", "https://dx.doi.org/10.1371/journal.pone.0098053.s015", "https://dx.doi.org/10.1371/journal.pone.0098053.s016"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Iqcg_Is_Essential_for_Sperm_Flagellum_Formation_in_Mice_/1033272", "title"=>"Iqcg Is Essential for Sperm Flagellum Formation in Mice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-05-21 03:18:33"}

PMC Usage Stats | Further Information

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Relative Metric

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