The ENU-induced cetus mutation reveals an essential role of the DNA helicase DDX11 for mesoderm development during early mouse embryogenesis.
BACKGROUND
DDX11 is a DNA helicase of the conserved FANCJ/RAD3/XPD family involved in maintaining genome stability. Studies in yeast and humans have shown requirements for DDX11 in sister chromatid cohesion and DNA repair. In mouse, loss of Ddx11 results in embryonic lethality. However, the developmental defects of Ddx11 mutants are poorly understood.


RESULTS
We describe the characterization and positional cloning of cetus, a mouse ENU-induced mutation in Ddx11. We demonstrate that cetus causes a nonconservative amino acid change in DDX11 motif V and that this mutation is a null allele of Ddx11. cetus mutant embryos failed to thrive beyond embryonic day 8.5 and displayed placental defects similar to those described in Ddx11 null embryos. Additionally, our characterization of Ddx11(cetus) mutants identified embryonic phenotypes that had not been previously reported in Ddx11(KO) embryos, including loss of somitic mesoderm, an open kinked neural tube and abnormal heart looping. We show that loss of Ddx11 causes widespread apoptosis from early embryonic stages and that loss of Ddx11 disrupts somitic mesoderm more dramatically than other embryonic cells.


CONCLUSIONS
Our results identify novel roles of Ddx11 during embryo morphogenesis and demonstrate that the activity of its motif V is essential for DDX11 function.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York.
Christina D
CD
Cota
María J
MJ
García-García
D020816:Amino Acid Motifs / Q000235:genetics / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D042822:Genomic Instability / Q000235:genetics; D008648:Mesoderm / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D009154:Mutation
C522421:ChlR1 protein, mouse; D053487:DEAD-box RNA Helicases