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Mouse: Ccdc8 KO

Technology #20-0031

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Yue Xiong
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To determine the mechanism underlying the 3-M syndrome, we knocked out Ccdc8 in the C57BL/6J mouse strain by standard homologous recombination methods. Ccdc8 conditional and conventional mice were generated by gene targeting in ES cells from C57BL/6 background strain microinjected into albino-C57BL/6 blastocysts. Successful Ccdc8 knockout was confirmed by Southern, PCR and DNA sequence. Deletion of Ccdc8 in mice cause perinatal lethality, intrauterine growth restriction, and placental defects. Heterozygous Ccdc8+/– mice are viable, fertile, and indistinguishable from wild-type littermates. We crossed heterozygous Ccdc8+/–mice and obtained no viable births of Ccdc8–/– mice. Ccdc8–/– embryos can be identified at late gestational stages up to E18.5, indicating that loss of Ccdc8 causes a perinatal lethality. At E18.5, Ccdc8–/– embryos were significantly smaller than heterozygous or wild-type embryos, indicating a growth restriction caused by the loss of Ccdc8as seen in 3-M syndrome patients.

Histological examination revealed that the placenta of Ccdc8–/– embryos is thinner than wild-type placenta and exhibits reduced branching of the maternal blood sinus in the labyrinth area. Ccdc8 is expressed in the labyrinth area, suggesting that the defects in the labyrinth area are directly caused by the loss of Ccdc8 function. Ccdc8 is also expressed in multiple tissues in the embryo, including the midbrain, hind-brain, pituitary, tongue, heart, cartilage primordium of the vertebral bodies, metanephros, and urogenital sinus. The growth restriction of Ccdc8-deficient embryos is likely caused by a combination of lack of adequate nutrients resulting from placental defects and additional defects in specific fetal tissues. Ccdc8–/– mouse embryo fibroblasts (MEFs) showed similar proliferation potential as Ccdc8+/+ MEFs.

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