In situ analysis of Raidd-beta-galactosidase fusion gene expression in transgenic mouse midgestation embryos.
Apoptosis and differentiation are tightly intertwined processes occurring at organ formation and remodelling during embryonic development. RAIDD (receptor-interacting protein [RIP]-associated ICH-1/CED-3-homologous protein with a death domain), a dual-domain adaptor protein has been shown to mediate the recruitment of CASPASE-2 to tumour necrosis factor receptor-1 (TNF-R1) signalling complex through RIP kinase. However, Raidd overexpression studies suggest that apart from the established role in apoptosis, Raidd may have an additional function in cell differentiation. In this study, we could not generate Raidd null adult mice suggesting that lack of function of Raidd might be embryonic lethal. Thus, to elucidate the role of Raidd during mouse embryogenesis when the processes of organogenesis are most dynamic, we studied the Raidd expression pattern in midgestation mouse embryos. We generated Raidd+/- transgenic mice with a reporter transgene encoding the bacterial Beta-galactosidase (beta-gal) under the control of Raidd promoter. During the midgestation period (E8.5-E12.5), Raidd is expressed in developing organs derived from the ectoderm such as lens, structures of the inner ear and the fourth brain ventricle in regions where differentiation takes place implicating Raidd role in this process. In addition, Raidd expression was found in developing mesenchyme organs like heart and kidney and in the endothelial lining of the midgut at the time when profound morphological changes take place in these organs. In developing heart and kidney Raidd expression patterns overlapped with known zones of cell death suggesting Raidd may be involved in apoptosis-mediated remodelling. The observed lethality of mice targeted at both Raidd alleles and Raidd expression patterns during midgestation period strongly suggest that Raidd plays an important role in mammalian development.
Motaln
H
H
University of Ljubljana, Biotechnical Faculty, Department of Animal Science, Groblje 3, 1230 Domzale, Slovenia.
McWhir
J
J
Horvat
S
S
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D019677:Artificial Gene Fusion; D001483:Base Sequence; D053420:CRADD Signaling Adaptor Protein; D017931:DNA Primers; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D006579:Heterozygote; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011247:Pregnancy; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D001616:beta-Galactosidase / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D053420:CRADD Signaling Adaptor Protein; C484481:Cradd protein, mouse; D017931:DNA Primers; D011993:Recombinant Fusion Proteins; D001616:beta-Galactosidase