Identification of Jade1 , a Gene Encoding a PHD Zinc Finger Protein, in a Gene Trap Mutagenesis Screen for Genes Involved in Anteroposterior Axis Development

Abstract

ABSTRACT In a gene trap screen for genes expressed in the primitive streak and tail bud during mouse embryogenesis, we isolated a mutation in Jade1 , a gene encoding a PHD zinc finger protein previously shown to interact with the tumor suppressor pVHL. Expressed sequence tag analysis indicates that Jade1 is subject to posttranscriptional regulation, resulting in multiple transcripts and at least two protein isoforms. The fusion Jade1-β-galactosidase reporter produced by the gene trap allele exhibits a regulated expression during embryogenesis and localizes to the nucleus and/or cytoplasm of different cell types. In addition to the primitive streak and tail bud, β-galactosidase activity was found in other embryonic regions where pluripotent or tissue-specific progenitors are known to reside, including the early gastrulation epiblast and the ventricular zone of the cerebral cortex. Prominent reporter expression was also seen in the extraembryonic tissues as well as other differentiated cell types in the embryo, in particular the developing musculature. We show that the gene trap mutation produces a null allele. However, homozygotes for the gene trap integration are viable and fertile. Database searches identified a family of Jade proteins conserved through vertebrates. This raises the possibility that the absence of phenotype is due to a functional compensation by other family members.