SummaryThe Bambi (Bmp and activin membrane-bound inhibitor) gene encodes a transmembrane protein highly similar in amino acid sequence to TGF-beta type-I receptors. Unlike the TGF-beta receptors, however, the Bambi intracellular domain is short and lacks a serine/threonine-kinase domain that is essential for transducing TGF-beta signaling. Previous biochemical assays showed that Bambi interacts directly with BMP receptors and antagonizes BMP signaling. Interestingly, the expression of Bambi largely overlaps, both temporally and spatially, with that of Bmp4 during early embryonic development in Xenopus, zebrafish, and mice, which led to the hypothesis that Bambi may function to regulate BMP signaling during embryogenesis. To directly analyze the roles of Bambi during embryonic development, we generated mice carrying a conditional allele of Bambi, Bambi flox , with loxP sequences flanking the first exon that encodes the N-terminus and signal peptide region of the Bambi protein. Mice homozygous for this targeted conditional allele appear normal and fertile. We crossed the Bambi flox/+ mice to the EIIa-Cre transgenic mice and generated mice carrying deletion of the first exon of the Bambi gene. Surprisingly, mice homozygous for the deleted allele were viable, fertile and didn't exhibit any discernible developmental defect. Our data exclude an essential role for Bambi in mouse embryonic development and postnatal survival.
KeywordsBambi; BMP signaling; Conditional knockout; Cre/loxP The transforming growth factor-beta (TGFβ) superfamily of secreted signaling molecules, including TGFβs, bone morphogenetic proteins (BMPs), and activins, plays essential roles throughout animal development. These molecules initiate cellular signaling by binding to and bringing together two types of receptor serine/threonine kinases. Upon ligand binding, the type-II receptor phosporylates and activates the type-I receptor kinase, which in turn phosphorylates and activates a set of transcriptional co-activators called Smad proteins and leads to their nuclear translocation and transcriptional activation of downstream target genes (reviewed in Shi and Massague, 2003;Nohe et al., 2004). In an expression screen for components involved in BMP4 signaling in Xenopus embryos, Onichtchouk et al. (1999) identified a gene encoding a transmembrane protein highly related to type-I TGFβ receptors. They named the gene product BAMBI (BMP and activin membrane-bound inhibitor) because it lacked an intracellular kinase domain and its overexpression antagonized BMP and activin signaling in Xenopus embryos (Onichtchouk et al., 1999 (Degen et al., 1996), Zebrafish (Tsang et al., 2000, mouse (Grotewold et al., 2001), and rat (Loveland et al., 2003).Ectopic expression of Bambi mRNA in Xenopus and zebrafish embryos resulted in phenotypes resembling inhibition of BMP signaling (Onichtchouk et al., 1999;Tsang et al., 2000). In vitro biochemical assays showed that the Bambi protein associated with type-I and type-II BMP/ TGFβ receptor complexes in the presence of liga...