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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: Publikationen MPI-CBG 2010-arch     Display Documents



ID: 546629.0, MPI für molekulare Zellbiologie und Genetik / Publikationen MPI-CBG 2010-arch
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, Jaroslaw; Fish, Jennifer L.; Wilsch-Bräuninger, Michaela; Arai, Yoko; Schreier, Dora; Naumann, Ronald; Helppi, Jussi; Habermann, Bianca; Vogt, Johannes; Nitsch, Robert; Toth, Attila; Enard, Wolfgang; Pääbo, Svante; Huttner, Wieland B.
Date of Publication (YYYY-MM-DD):2010
Title of Journal:Proceedings of the National Academy of Sciences of the United States of America
Volume:107
Issue / Number:38
Start Page:16595
End Page:16600
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
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.
External Publication Status:published
Document Type:Article
Communicated by:nn
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:4157
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