Author/Editor | Motaln, Helena | |
Title | Vloga gena Raidd med embrionalnim razvojem miši (Mus musculus) | |
Translated title | The role of Raidd gene during embryonic development of the mouse (Mus musculus) | |
Type | monografija | |
Place | Ljubljana | |
Publisher | Univerza v Ljubljani, Medicinska fakulteta | |
Publication year | 2004 | |
Volume | str. 177 | |
Language | slo | |
Abstract | Apoptosis, a form of programmed cell death has been observed during embryogenesis both in vivo and in vitro in a wide range of mammalian species. RAIDD, a dual-domain adaptor protein, has been shown to mediate the recruitment of Caspase-2 to tumour necrosis factor receptor I (TNFR-1) signalling complex through RIP kinaze. Raidd over-expression studies suggest that apart from the established role in the cascade of apoptotic pathway, Raidd may have additional function in the process of cell differentiation during development. Mechanisms by which Raidd acts in apoptosis/differentiation are not fully understood yet, thus we attempted to illuminate this by characterizing Raidd deficient mice. In our first study, we utilized a transgenic model, Raidd/beta-geo+/- mouse line carrying a reporter transgene (beta-gaI) under the control of Raidd promoter. These mice were used for in situ analysis of Raidd expression in different tissues of midgestation embryos E8,5 - E12,5, when organogenesis is most dynamic. Expression analysis revealed that spatial change in Raidd expression is stage and tissue/organ specific, which was later confirmed with immunohistochemistry of pre- and postnatal stages. In addition, inability to identify homozygous Raidd/beta-geo-/- pups among 88 neonates examined, underpinned the hypothesis of Raidd's essential role during embryonic development. Further genotype analysis of over 200 embryos revealed a selective absence of Raidd-/- individuals at E10.5 of gestation down to day 1.5 pc of pre-implantation development. The ratio of wild type to Raidd-/+ individuals from the intercrosses remained 1:2, implying that Raidd homozygous null allele causes in vivo preimplantation lethality prior to 2-cell stage. (Abstract truncated at 2000 characters). | |
Descriptors | EMBRYO FETAL DEVELOPMENT APOPTOSIS CELL CYCLE PROTEINS CHIMERA PHENOTYPE HOMOZYGOTE HETEROZYGOTE MICE, TRANSGENIC MICE, KNOCKOUT PLASMIDS RECOMBINATION, GENETIC IMMUNOHISTOCHEMISTRY GENOTYPE |