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Molecular and Cellular Biology, July 2004, p. 5863-5874, Vol. 24, No. 13
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.13.5863-5874.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Nuclear Scaffold Protein NIPP1 Is Essential for Early Embryonic Development and Cell Proliferation

Aleyde Van Eynde,^1, Mieke Nuytten,^1, Mieke Dewerchin,² Luc Schoonjans,³ Stefaan Keppens,¹ Monique Beullens,¹ Lieve Moons,² Peter Carmeliet,² Willy Stalmans,¹ and Mathieu Bollen¹

Division of Biochemistry,¹ Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Faculty of Medicine, Catholic University of Leuven,² Thromb-X NV, B-3000 Leuven, Belgium³

Received 23 January 2004/ Accepted 3 April 2004

NIPP1 (nuclear inhibitor of protein phosphatase 1) is a ubiquitously expressed nuclear scaffold protein that has been implicated in both transcription and RNA processing. Among its protein ligands are a protein kinase, a protein phosphatase, two splicing factors, and a transcriptional regulator, and the binding of these proteins to NIPP1 is tightly regulated by phosphorylation. To study the function of NIPP1 in vivo, we have used homologous recombination to generate mice that are deficient in NIPP1. NIPP1^–/+ mice developed normally. However, NIPP1^–/– embryos showed severely retarded growth at embryonic day 6.5 (E6.5) and were resorbed by E8.5. This early embryonic lethality was not associated with increased apoptosis but correlated with impaired cell proliferation. Blastocyst outgrowth experiments and the RNA interference-mediated knockdown of NIPP1 in cultured cells also revealed an essential role for NIPP1 in cell proliferation. In further agreement with this function, no viable NIPP1^–/– cell lines were obtained by derivation of embryonic stem (ES) cells from blastocysts of NIPP1^–/+ intercrosses or by forced homogenotization of heterozygous ES cells at high concentrations of Geneticin. We conclude that NIPP1 is indispensable for early embryonic development and cell proliferation.

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* Corresponding author. Mailing address: Afdeling Biochemie, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. Phone: 32-16-34 57 01. Fax: 32-16-34 59 95. E-mail: Aleyde.VanEynde{at}med.kuleuven.ac.be.

A.V.E. and M.N. contributed equally to this work.

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Molecular and Cellular Biology, July 2004, p. 5863-5874, Vol. 24, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.13.5863-5874.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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