{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T03:22:33Z","timestamp":1793762553962,"version":"4.6.1"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"38","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,9,21]]},"abstract":"<jats:p>\n                    Mutations in\n                    <jats:italic>ASPM<\/jats:italic>\n                    (abnormal spindle-like microcephaly associated) cause primary microcephaly in humans, a disorder characterized by a major reduction in brain size in the apparent absence of nonneurological anomalies. The function of the Aspm protein in neural progenitor cell expansion, as well as its localization to the mitotic spindle and midbody, suggest that it regulates brain development by a cell division-related mechanism. Furthermore, evidence that positive selection affected\n                    <jats:italic>ASPM<\/jats:italic>\n                    during primate evolution has led to suggestions that such a function changed during primate evolution. Here, we report that in\n                    <jats:italic>Aspm<\/jats:italic>\n                    mutant mice, truncated Aspm proteins similar to those causing microcephaly in humans fail to localize to the midbody during M-phase and cause mild microcephaly. A human\n                    <jats:italic>ASPM<\/jats:italic>\n                    transgene rescues this phenotype but, interestingly, does not cause a gain of function. Strikingly, truncated Aspm proteins also cause a massive loss of germ cells, resulting in a severe reduction in testis and ovary size accompanied by reduced fertility. These germline effects, too, are fully rescued by the human\n                    <jats:italic>ASPM<\/jats:italic>\n                    transgene, indicating that ASPM is functionally similar in mice and humans. Our findings broaden the spectrum of phenotypic effects of\n                    <jats:italic>ASPM<\/jats:italic>\n                    mutations and raise the possibility that positive selection of\n                    <jats:italic>ASPM<\/jats:italic>\n                    during primate evolution reflects its function in the germline.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1010494107","type":"journal-article","created":{"date-parts":[[2010,9,7]],"date-time":"2010-09-07T22:21:32Z","timestamp":1283898092000},"page":"16595-16600","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":178,"title":["Mutations in mouse\n                    <i>Aspm<\/i>\n                    (abnormal spindle-like microcephaly associated) cause not only microcephaly but also major defects in the germline"],"prefix":"10.1073","volume":"107","author":[{"given":"Jeremy N.","family":"Pulvers","sequence":"first","affiliation":[{"name":"Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw","family":"Bryk","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Fish","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Wilsch-Br\u00e4uninger","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Arai","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora","family":"Schreier","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Naumann","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussi","family":"Helppi","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Habermann","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Vogt","sequence":"additional","affiliation":[{"name":"Institute for Cell Biology and Neurobiology, Center for Anatomy, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, 10115 Berlin, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Nitsch","sequence":"additional","affiliation":[{"name":"Institute for Cell Biology and Neurobiology, Center for Anatomy, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, 10115 Berlin, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Enard","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svante","family":"P\u00e4\u00e4bo","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wieland B.","family":"Huttner","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,9,7]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2719"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2008"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.023465"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2004.01.003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng995"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2005.04.009"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/165.4.2063"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020126"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116815"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2009.03.013"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604066103"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi220"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.6.13.4356"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/379085"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.062380"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181b8799a"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(02)00253-8"},{"key":"e_1_3_3_18_2","first-page":"301","article-title":"Expression analysis of the autosomal recessive primary microcephaly genes MCPH1 (microcephalin) and MCPH5 (ASPM, abnormal spindle-like, microcephaly associated) in human malignant gliomas","volume":"20","author":"Hagemann C","year":"2008","unstructured":"C Hagemann, et al., Expression analysis of the autosomal recessive primary microcephaly genes MCPH1 (microcephalin) and MCPH5 (ASPM, abnormal spindle-like, microcephaly associated) in human malignant gliomas. 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