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First published online 21 January 2004
doi: 10.1242/dev.00973
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1 Department of Molecular Cell Biology, Research Institute for Microbial
Diseases, Osaka University, 3-1 Yamada-oka, Suita-shi, Osaka 565-0871,
Japan
2 Laboratory of Cytogenetics, Division of Bioscience, Graduate School of
Environmental Earth Science, Hokkaido University, North 10, West 8, Kita-ku,
Sapporo 060-0810, Japan
3 Laboratory of Animal Cytogenetics, Center for Advanced Science and Technology,
Hokkaido University, North 10, West 8, Kita-ku, Sapporo 060-0810, Japan
4 Department of Laboratory Sciences for Animal Experimentation, Research
Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita-shi,
Osaka 565-0871, Japan
5 Department of Cell Biology, Duke University Medical Center, PO Box 3709, DUMC,
Durham, NC 27710, USA
* Author for correspondence (e-mail: tnakano{at}biken.osaka-u.ac.jp)
Accepted 7 November 2003
The piwi family genes, which are defined by conserved PAZ and Piwi domains, play important roles in stem cell self-renewal, RNA silencing, and translational regulation in various organisms. To reveal the function of the mammalian homolog of piwi, we produced and analyzed mice with targeted mutations in the Mili gene, which is one of three mouse homologs of piwi. Spermatogenesis in the MILI-null mice was blocked completely at the early prophase of the first meiosis, from the zygotene to early pachytene, and the mice were sterile. However, primordial germ cell development and female germ cell production were not disturbed. Furthermore, MILI bound to MVH, which is an essential factor during the early spermatocyte stage. The similarities in the phenotypes of the MILI- and MVH-deficient mice and in the physical binding properties of MILI and MVH indicate a functional association of these proteins in post-transcriptional regulation. These data indicate that MILI is essential for the differentiation of spermatocytes.
Key words: Mili, Miwi, piwi, Mvh, Spermatogenesis
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