International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

I13. Lethality of qkI Null Embryos is due to Failure in Embryonic Blood Vessel Development

Li, S1., Takakura, N1., Oike, Y1., Suda, T1., Artzt, K2., Yamamura, K1. and Abe, K1
1Inst. Mol. Embryol. & Genet., Kumamoto Univ., Japan.;
Inst. Cell & Mol. Biol., Univ. Texas at Austin.

qkI encodes a KH domain RNA binding protein that has been isolated as a candidate for classical neurological mutation, quaking viable (qkv). qkI is considered as an essential regulator of myelination in CNS of the mice. However, qkI homologs in other species play important roles in various developmental processes other than myelination. Here we show that a novel function of the qkI in embryonic development through the analysis of the targeted null mutation of qkI. We found that homozygous embryos died in utero. At E8.5, some of the homozygotes had a wavy neural tube. At E9.5, all of the homozygotes exhibited a kinked neural tube, a severe pericardial effusion, and somites of abnormal shape. Some of the homozygous embryos showed defects in neural tube closure. All of the homozygotes die by E10.5. Since pericardial effusion is often an indication of yolk sac circulation abnormality, we have analyzed blood vessel formation in the qkI null embryos. It was found that only very thin vitelline artery was formed and it did not connect properly to yolk sac, thereby preventing remodeling of yolk sac vasculature. Therefore the lethality of qkI-/- embryos is primarily due to this defect in vitello-embryo connection. Both in vivo and in vitro analyses of qkI-/- embryos suggested that the vitellin vessel was deficient in smooth muscle cells (SMC), which is required for stabilization of the blood vessel structures and modulation of their functions. Addition of the flow sorted QKI+ SMC into an in vitro culture of qkI-/- paraaortic splanchnopleural explant rescued the vascular remodeling deficit. These findings suggest that QKI RNA binding protein has a critical regulatory role in SMC development, or interactions between SMC and vascular endothelial cells and matrix.

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