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This version published online on March 20, 2007
Molecular Endocrinology, doi:10.1210/me.2007-0052
A more recent version of this article appeared on June 1, 2007
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Submitted on January 26, 2007
Accepted on March 15, 2007

An ATPase of the SNF2 Family, Androgen Receptor-Interacting Protein 4 (ARIP4), Is Essential for Mouse Embryonic Development and Cell Proliferation

Fu-Ping Zhang, Andrii Domanskyi, Jorma J. Palvimo, Hannu Sariola, Juha Partanen, and Olli A. Jänne*

Biomedicum Helsinki (F.-P.Z., A.D., J.J.P., O.A.J.), Institute of Biomedicine (Physiology), University of Helsinki, FI-00014, Helsinki, Finland; Department of Medical Biochemistry (J.J.P.), University of Kuopio, FI-70211 Kuopio, Finland; Biomedicum Helsinki (H.S.), Institute of Biomedicine (Developmental Biology), University of Helsinki, FI-00014, Helsinki, Finland; Developmental Biology Program (J.P.), Institute of Biotechnology, University of Helsinki, Finland; Department of Clinical Chemistry (O.A.J.), Helsinki University Central Hospital, FI-00290 Helsinki, Finland

* To whom correspondence should be addressed. E-mail: olli.janne{at}helsinki.fi.

An ATPase of the SNF2 protein family, ARIP4 (androgen receptor-interacting protein 4), modulates androgen receptor activity. To elucidate receptor-dependent and -independent functions of ARIP4, we have analyzed Arip4 gene-targeted mice. Heterozygous Arip4 mutants were normal. Arip4 is expressed mainly in the neural tube and limb buds during early embryonic development. Arip4-/- embryos were abnormal already at embryonic day (E) 9.5 and died by E11.5. At E9.5 and 10.5, almost all major tissues of Arip4 null embryos were proportionally smaller than those of wild-type embryos, and the neural tube was shrunk in some Arip4-/- embryos. Dramatically reduced cell proliferation and increased apoptosis were observed in E9.5 and E10.5 Arip4 null embryos. Mouse embryonic fibroblasts (MEFs) isolated from Arip4-/- embryos ceased to grow after 2-3 passages and exhibited increased apoptosis and decreased DNA synthesis compared to wild-type MEFs. Comparison of gene-expression profiles of Arip4-/- and wild-type MEFs at E9.5 revealed that putative ARIP4 target genes are involved in cell growth and proliferation, apoptosis, cell death, DNA replication and repair, and development. Collectively, ARIP4 plays an essential role in mouse embryonic development and cell proliferation, and it appears to coordinate multiple essential biological processes, possibly through a complex chromatin remodeling system.
Key words: androgen receptor • gene-trap • ATPase • proliferation • embryogenesis

NURSA Molecule Pages Link:

Coregulators:   ARIP4





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