The biological function of regulatory factor X1 (RFX1), the prototype member of the transcription factor RFX family, is not clear. We have used gene trap technique to disrupt the expression of RFX1 in mice. Although, heterozygous RFX1(+/-) mice appear normal and fertile, homozygous RFX1(-/-) embryos died at an early stage (most likely before embryonic day 2.5). Our results indicate that RFX1 regulates expression of genes that are essential for early embryonic development/survival and that RFX1 function can not be compensated by other RFX1 family members. (C) 2009 Elsevier Inc. All rights reserved.