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Taken together, these observations suggested that the KIN5 knockdown phenotype produced loss of normal coordinated movement and then lethality, which is consistent with our earlier finding that KIN5 is an essential gene.
Synthetic lethality, which is caused by a combination of two genetic mutations that lead to cell death, is one emerging strategy for molecular targeted cancer therapy [20].
Ten of the 48 genes in these pathways were associated with postnatal growth retardation or postnatal lethality, which is substantially influenced by maternal/lactation performance.
The ex vivo development and transparency of zebrafish embryos further enable their use for studying early developmental genes associated with embryonic lethality, which is a bottleneck in mouse models.
Constitutive depletion of the mouse HIF1α gene (HIF1α−/−) results in developmental arrest and embryonic lethality, which is characterized by neural tube defects, cardiovascular malformations, dysregulated erythropoiesis signaling, and marked cell death within the cephalic mesenchyme.
The analysis of Map3k1 mPHD mice has been complicated by their early embryonic lethality, which is a more severe phenotype than the partial lethality observed in Map3k1 ΔKD mice (Bonnesen et al, 2005).
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Using a combination of previously mapped and newly developed genetic markers, we identified three chromosome regions associated with these two types of lethality, which were genetically independent.
In particular, microinjection of siRNA against the abundant pancRNA partner of interleukin 17d (Il17d) mRNA at the 1-cell stage caused embryonic lethality, which was rescued by supplying IL17D protein in vitro at the 4-cell stage.
The ectopic expression of miR-203 in the basal layer of mouse skin resulted in perinatal lethality, which was associated with a lack of epidermal basal progenitors and the detection of sporadic ΔNp63-expressing cells.
As seen in Table 1, we selected the bacterial dose that resulted in a phenotypic change in 10 days with the least lethality (which was 2.4 x 10 bacterial cells/day/100 ml lake water for 10 days).
A similar phenotype has been reported for Nedd4-2 −/− mice, in which the targeted homozygous nulls in the C57BL/6J background exhibit almost complete neonatal lethality, which was partially rescued by crossing into the same mixed genetic background as our mice (Boase et al. 2011).
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