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Human Molecular Genetics Advance Access originally published online on August 22, 2006
Human Molecular Genetics 2006 15(19):2936-2944; doi:10.1093/hmg/ddl235
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Targeted disruption of the synovial sarcoma-associated SS18 gene causes early embryonic lethality and affects PPARBP expression

D.R.H. de Bruijn1, W.J.M. Peters1, S.M. Chuva de Sousa Lopes3, A.H.A. van Dijk1, M.P. Willemse1, R. Pfundt1, P. de Boer2 and A. Geurts van Kessel1,*

1 Department of Human Genetics and 2 Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands and 3 Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK

* To whom correspondence should be addressed. Tel: +31 243614107; Fax: +31 243668752; Email: a.geurtsvankessel{at}antrg.umcn.nl

Received June 16, 2006; Accepted August 13, 2006

The synovial sarcoma-associated protein SS18 (also known as SYT or SSXT) is thought to act as a transcriptional co-activator. This activity appears to be mediated through the SWI/SNF proteins BRG1 and INI1 and the histone acetyl transferase p300. Here, we report that disruption of the mouse Ss18 gene results in a recessive embryonic lethal phenotype, due to placental failure caused by impairment of placental vascularization and/or chorio-allantoic fusion. This phenotype resembles the p300 knockout phenotype, but is distinct from the Brg1 and Ini1 knockout phenotypes. Through expression profiling of knockout embryos, we observed altered expression of genes known to affect placental development, including the peroxisome proliferator-activated receptor-binding protein (Pparbp). Since Pparbp null mutant embryos display a similar, lethal phenotype with placental failure, we suggest that the functional and phenotypic co-linearities between Ss18 and p300 may also include the transcriptional co-activator Pparbp. Additional interbreeding of Ss18 and Ss18l1 (Crest) mutant mice indicates that these two functionally and structurally related genes may act synergistically during critical stages of embryonic development.


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