Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta
Spermatogenesis is a complex process that involves cooperation of germ cells and testicular somatic cells. Various genetic disorders lead to impaired spermatogenesis, defective sperm function and male infertility 1 . Here we show that Cnot7 −/− males are sterile owing to oligo-astheno-teratozoosperm...
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| Veröffentlicht in: | Nature genetics 2004-05, Vol.36 (5), p.528-533 |
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| container_title | Nature genetics |
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| creator | Nakamura, Takahisa Yao, Ryoji Ogawa, Takehiko Suzuki, Toru Ito, Chizuru Tsunekawa, Naoki Inoue, Kimiko Ajima, Rieko Miyasaka, Takashi Yoshida, Yutaka Ogura, Atsuo Toshimori, Kiyotaka Noce, Toshiaki Yamamoto, Tadashi Noda, Tetsuo |
| description | Spermatogenesis is a complex process that involves cooperation of germ cells and testicular somatic cells. Various genetic disorders lead to impaired spermatogenesis, defective sperm function and male infertility
1
. Here we show that
Cnot7
−/−
males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor
2
, is essential for spermatogenesis. Maturation of spermatids is unsynchronized and impaired in seminiferous tubules of
Cnot7
−/−
mice. Transplantation of spermatogonial stem cells from male
Cnot7
−/−
mice to seminiferous tubules of
Kit
mutant mice (
Kit
W/W-v
) restores spermatogenesis, suggesting that the function of testicular somatic cells is damaged in the
Cnot7
−/−
condition. The testicular phenotypes of
Cnot7
−/−
mice are similar to those of mice deficient in retinoid X receptor beta (
Rxrb
)
3
. We further show that Cnot7 binds the AF-1 domain of Rxrb and that Rxrb malfunctions in the absence of Cnot7. Therefore, Cnot7 seems to function as a coregulator of Rxrb in testicular somatic cells and is thus involved in spermatogenesis. |
| doi_str_mv | 10.1038/ng1344 |
| format | Article |
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1
. Here we show that
Cnot7
−/−
males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor
2
, is essential for spermatogenesis. Maturation of spermatids is unsynchronized and impaired in seminiferous tubules of
Cnot7
−/−
mice. Transplantation of spermatogonial stem cells from male
Cnot7
−/−
mice to seminiferous tubules of
Kit
mutant mice (
Kit
W/W-v
) restores spermatogenesis, suggesting that the function of testicular somatic cells is damaged in the
Cnot7
−/−
condition. The testicular phenotypes of
Cnot7
−/−
mice are similar to those of mice deficient in retinoid X receptor beta (
Rxrb
)
3
. We further show that Cnot7 binds the AF-1 domain of Rxrb and that Rxrb malfunctions in the absence of Cnot7. Therefore, Cnot7 seems to function as a coregulator of Rxrb in testicular somatic cells and is thus involved in spermatogenesis.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng1344</identifier><identifier>PMID: 15107851</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Agriculture ; Animal Genetics and Genomics ; Animals ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cell differentiation, maturation, development, hematopoiesis ; Cell physiology ; Cell receptors ; Cell structures and functions ; Chromatin Assembly Factor-1 ; Chromosomal Proteins, Non-Histone - genetics ; Chromosomal Proteins, Non-Histone - physiology ; COS Cells ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - physiology ; Female ; Fibroblasts ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation ; Gene Function ; Genetic aspects ; Human Genetics ; In vitro fertilization ; Infertility ; Kinases ; letter ; Male ; Males ; Medical research ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Nude ; Miscellaneous ; Molecular and cellular biology ; Morphology ; Motility ; Oligospermia - complications ; Oligospermia - etiology ; Oligospermia - genetics ; Phenotype ; Physiological aspects ; Proto-Oncogene Proteins c-kit - genetics ; Proto-Oncogene Proteins c-kit - physiology ; Retinoids ; Seminiferous Tubules - metabolism ; Sperm ; Sperm Motility ; Spermatogenesis ; Spermatogenesis - genetics ; Spermatozoa - abnormalities ; Stem Cell Transplantation ; Stem cells ; Teratogenesis</subject><ispartof>Nature genetics, 2004-05, Vol.36 (5), p.528-533</ispartof><rights>Springer Nature America, Inc. 2004</rights><rights>2004 INIST-CNRS</rights><rights>COPYRIGHT 2004 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c628t-6f1e472e0e3f34c9d32349928ac5e5d986d535a67e5627501cc71411be3f32453</citedby><cites>FETCH-LOGICAL-c628t-6f1e472e0e3f34c9d32349928ac5e5d986d535a67e5627501cc71411be3f32453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ng1344$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ng1344$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15783432$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15107851$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nakamura, Takahisa</creatorcontrib><creatorcontrib>Yao, Ryoji</creatorcontrib><creatorcontrib>Ogawa, Takehiko</creatorcontrib><creatorcontrib>Suzuki, Toru</creatorcontrib><creatorcontrib>Ito, Chizuru</creatorcontrib><creatorcontrib>Tsunekawa, Naoki</creatorcontrib><creatorcontrib>Inoue, Kimiko</creatorcontrib><creatorcontrib>Ajima, Rieko</creatorcontrib><creatorcontrib>Miyasaka, Takashi</creatorcontrib><creatorcontrib>Yoshida, Yutaka</creatorcontrib><creatorcontrib>Ogura, Atsuo</creatorcontrib><creatorcontrib>Toshimori, Kiyotaka</creatorcontrib><creatorcontrib>Noce, Toshiaki</creatorcontrib><creatorcontrib>Yamamoto, Tadashi</creatorcontrib><creatorcontrib>Noda, Tetsuo</creatorcontrib><title>Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Spermatogenesis is a complex process that involves cooperation of germ cells and testicular somatic cells. Various genetic disorders lead to impaired spermatogenesis, defective sperm function and male infertility
1
. Here we show that
Cnot7
−/−
males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor
2
, is essential for spermatogenesis. Maturation of spermatids is unsynchronized and impaired in seminiferous tubules of
Cnot7
−/−
mice. Transplantation of spermatogonial stem cells from male
Cnot7
−/−
mice to seminiferous tubules of
Kit
mutant mice (
Kit
W/W-v
) restores spermatogenesis, suggesting that the function of testicular somatic cells is damaged in the
Cnot7
−/−
condition. The testicular phenotypes of
Cnot7
−/−
mice are similar to those of mice deficient in retinoid X receptor beta (
Rxrb
)
3
. We further show that Cnot7 binds the AF-1 domain of Rxrb and that Rxrb malfunctions in the absence of Cnot7. Therefore, Cnot7 seems to function as a coregulator of Rxrb in testicular somatic cells and is thus involved in spermatogenesis.</description><subject>Agriculture</subject><subject>Animal Genetics and Genomics</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell physiology</subject><subject>Cell receptors</subject><subject>Cell structures and functions</subject><subject>Chromatin Assembly Factor-1</subject><subject>Chromosomal Proteins, Non-Histone - genetics</subject><subject>Chromosomal Proteins, Non-Histone - physiology</subject><subject>COS Cells</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - physiology</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation</subject><subject>Gene Function</subject><subject>Genetic aspects</subject><subject>Human Genetics</subject><subject>In vitro fertilization</subject><subject>Infertility</subject><subject>Kinases</subject><subject>letter</subject><subject>Male</subject><subject>Males</subject><subject>Medical research</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mice, Nude</subject><subject>Miscellaneous</subject><subject>Molecular and cellular biology</subject><subject>Morphology</subject><subject>Motility</subject><subject>Oligospermia - complications</subject><subject>Oligospermia - etiology</subject><subject>Oligospermia - genetics</subject><subject>Phenotype</subject><subject>Physiological aspects</subject><subject>Proto-Oncogene Proteins c-kit - genetics</subject><subject>Proto-Oncogene Proteins c-kit - physiology</subject><subject>Retinoids</subject><subject>Seminiferous Tubules - metabolism</subject><subject>Sperm</subject><subject>Sperm Motility</subject><subject>Spermatogenesis</subject><subject>Spermatogenesis - genetics</subject><subject>Spermatozoa - abnormalities</subject><subject>Stem Cell Transplantation</subject><subject>Stem cells</subject><subject>Teratogenesis</subject><issn>1061-4036</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN0luL1DAUAOAgiruO-hOkKCqCXXNt0sdl8LKwMOANXyRk0tOatU3GJAX115syA-ssPkgecvuSk8tB6CHBZwQz9coPhHF-C50SwZuaSKJulzZuSM0xa07QvZSuMCacY3UXnRBBsFSCnKKvm9ENoTYpfwMf6gzR5PA7hLSDODlTOV9NzkI1Gvvd-aFa-5Dly8pUEYZ5LDZWoS-d7HxwXfWlNC3sluEtZHMf3enNmODBoV6hT29ef1y_qy83by_W55e1bajKddMT4JICBtYzbtuOUcbblipjBYiuVU0nmDCNBNFQKTCxVhJOyHbxlAu2Qs_2--5i-DFDynpyycI4Gg9hTprIVlGpVIGPb8CrMEdfzqYppY0QhC7oyR4NZgTtfB9yNHbZUZ8TxUpg2i7q7B-qlA7KiwUPvSvjRwteHC0oJsPPPJg5JX3x4f3_283nY3u4vI0hpQi93kU3mfhLE6yX5ND75Cjw0eHy83aC7podsqGApwdgkjVjH423Lv3lZAla_maFnu9dKlN-gHj9ijdC_gEIMMjY</recordid><startdate>20040501</startdate><enddate>20040501</enddate><creator>Nakamura, Takahisa</creator><creator>Yao, Ryoji</creator><creator>Ogawa, Takehiko</creator><creator>Suzuki, Toru</creator><creator>Ito, Chizuru</creator><creator>Tsunekawa, Naoki</creator><creator>Inoue, Kimiko</creator><creator>Ajima, Rieko</creator><creator>Miyasaka, Takashi</creator><creator>Yoshida, Yutaka</creator><creator>Ogura, Atsuo</creator><creator>Toshimori, Kiyotaka</creator><creator>Noce, Toshiaki</creator><creator>Yamamoto, Tadashi</creator><creator>Noda, Tetsuo</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope></search><sort><creationdate>20040501</creationdate><title>Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta</title><author>Nakamura, Takahisa ; Yao, Ryoji ; Ogawa, Takehiko ; Suzuki, Toru ; Ito, Chizuru ; Tsunekawa, Naoki ; Inoue, Kimiko ; Ajima, Rieko ; Miyasaka, Takashi ; Yoshida, Yutaka ; Ogura, Atsuo ; Toshimori, Kiyotaka ; Noce, Toshiaki ; Yamamoto, Tadashi ; Noda, Tetsuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c628t-6f1e472e0e3f34c9d32349928ac5e5d986d535a67e5627501cc71411be3f32453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Agriculture</topic><topic>Animal Genetics and Genomics</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell physiology</topic><topic>Cell receptors</topic><topic>Cell structures and functions</topic><topic>Chromatin Assembly Factor-1</topic><topic>Chromosomal Proteins, Non-Histone - genetics</topic><topic>Chromosomal Proteins, Non-Histone - physiology</topic><topic>COS Cells</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - physiology</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation</topic><topic>Gene Function</topic><topic>Genetic aspects</topic><topic>Human Genetics</topic><topic>In vitro fertilization</topic><topic>Infertility</topic><topic>Kinases</topic><topic>letter</topic><topic>Male</topic><topic>Males</topic><topic>Medical research</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mice, Nude</topic><topic>Miscellaneous</topic><topic>Molecular and cellular biology</topic><topic>Morphology</topic><topic>Motility</topic><topic>Oligospermia - complications</topic><topic>Oligospermia - etiology</topic><topic>Oligospermia - genetics</topic><topic>Phenotype</topic><topic>Physiological aspects</topic><topic>Proto-Oncogene Proteins c-kit - genetics</topic><topic>Proto-Oncogene Proteins c-kit - physiology</topic><topic>Retinoids</topic><topic>Seminiferous Tubules - metabolism</topic><topic>Sperm</topic><topic>Sperm 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Tetsuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2004-05-01</date><risdate>2004</risdate><volume>36</volume><issue>5</issue><spage>528</spage><epage>533</epage><pages>528-533</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><coden>NGENEC</coden><abstract>Spermatogenesis is a complex process that involves cooperation of germ cells and testicular somatic cells. Various genetic disorders lead to impaired spermatogenesis, defective sperm function and male infertility
1
. Here we show that
Cnot7
−/−
males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor
2
, is essential for spermatogenesis. Maturation of spermatids is unsynchronized and impaired in seminiferous tubules of
Cnot7
−/−
mice. Transplantation of spermatogonial stem cells from male
Cnot7
−/−
mice to seminiferous tubules of
Kit
mutant mice (
Kit
W/W-v
) restores spermatogenesis, suggesting that the function of testicular somatic cells is damaged in the
Cnot7
−/−
condition. The testicular phenotypes of
Cnot7
−/−
mice are similar to those of mice deficient in retinoid X receptor beta (
Rxrb
)
3
. We further show that Cnot7 binds the AF-1 domain of Rxrb and that Rxrb malfunctions in the absence of Cnot7. Therefore, Cnot7 seems to function as a coregulator of Rxrb in testicular somatic cells and is thus involved in spermatogenesis.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>15107851</pmid><doi>10.1038/ng1344</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2004-05, Vol.36 (5), p.528-533 |
| issn | 1061-4036 1546-1718 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_17982788 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | Agriculture Animal Genetics and Genomics Animals Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Cell differentiation, maturation, development, hematopoiesis Cell physiology Cell receptors Cell structures and functions Chromatin Assembly Factor-1 Chromosomal Proteins, Non-Histone - genetics Chromosomal Proteins, Non-Histone - physiology COS Cells DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology Female Fibroblasts Fundamental and applied biological sciences. Psychology Gene Expression Regulation Gene Function Genetic aspects Human Genetics In vitro fertilization Infertility Kinases letter Male Males Medical research Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Nude Miscellaneous Molecular and cellular biology Morphology Motility Oligospermia - complications Oligospermia - etiology Oligospermia - genetics Phenotype Physiological aspects Proto-Oncogene Proteins c-kit - genetics Proto-Oncogene Proteins c-kit - physiology Retinoids Seminiferous Tubules - metabolism Sperm Sperm Motility Spermatogenesis Spermatogenesis - genetics Spermatozoa - abnormalities Stem Cell Transplantation Stem cells Teratogenesis |
| title | Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T12%3A36%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Oligo-astheno-teratozoospermia%20in%20mice%20lacking%20Cnot7,%20a%20regulator%20of%20retinoid%20X%20receptor%20beta&rft.jtitle=Nature%20genetics&rft.au=Nakamura,%20Takahisa&rft.date=2004-05-01&rft.volume=36&rft.issue=5&rft.spage=528&rft.epage=533&rft.pages=528-533&rft.issn=1061-4036&rft.eissn=1546-1718&rft.coden=NGENEC&rft_id=info:doi/10.1038/ng1344&rft_dat=%3Cgale_proqu%3EA183411298%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222655128&rft_id=info:pmid/15107851&rft_galeid=A183411298&rfr_iscdi=true |