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          Institute: MPI für Evolutionsbiologie     Collection: Evolutionary genetics     Display Documents

ID: 572151.0, MPI für Evolutionsbiologie / Evolutionary genetics
Mutations in mouse Aspm (abnormal spindle-like microcephaly associated) cause not only microcephaly but also major defects in the germline
Authors:Pulvers, Jeremy N.; Bryk, Jarosław; Fish, Jennifer L.; Wilsch-Bräuninger, Michaela; Arai, Yoko; Schreier, Dora; Naumann, Ronald; Helppi, Jussi; Habermann, Bianca; Vogt, Johannes; Nitsch, Robert; Tóth, Attila; Enard, Wolfgang; Pääbo, Svante; Huttner, Wieland B.
Date of Publication (YYYY-MM-DD):2010-09-21
Title of Journal:Proceedings of the National Academy of Sciences of the United States of America
Journal Abbrev.:PNAS
Issue / Number:38
Start Page:16595
End Page:16600
Review Status:not specified
Audience:Not Specified
Abstract / Description:Mutations in ASPM (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 ASPM during primate evolution has led to suggestions that such a function changed during primate evolution. Here, we report that in Aspm 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 ASPM 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 ASPM transgene, indicating that ASPM is functionally similar in mice and humans. Our findings broaden the spectrum of phenotypic effects of ASPM mutations and raise the possibility that positive selection of ASPM during primate evolution reflects its function in the germline.
Free Keywords:evolution; cerebral cortex; fertility; neural stem cells; germ cells
External Publication Status:published
Document Type:Article
Communicated by:Brigitte Lechner
Affiliations:MPI für Evolutionsbiologie/Abt. Evolutionsgenetik
External Affiliations:Max Planck Inst Evolutionary Anthropol, D-04103 Leipzig, Germany; Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany; Charite, Ctr Anat, Inst Cell Biol & Neurobiol, D-10115 Berlin, Germany; Tech Univ Dresden, Inst Physiol Chem, D-01307 Dresden, Germany
Identifiers:ISSN:0027-8424 (print) [ID-No:1]
ISSN:1091-6490 (online) [ID-No:2]
DOI:10.1073/pnas.1010494107 [ID-No:3]
LOCALID:2864/S 39207 [Listen-Nummer/S-Nummer]
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