Localization and identification of the mutant gene in the loop-tail mouse / 中国比较医学杂志

Objective To define the loci of the mutant gene in the loop-tail mouse.Methods To study the heredity pattern, loop-tail mice were mated with normal C57BL/6J and C3H mice.Their offsprings with loop-tail or normal phenotype were registered respectively.Microsatellite marker D1Mit113 and D1Mit149 were used to locate the mutant gene.Based on fine mapping, the candidate gene Vangl2 was found.Vangl2 gene from the loop-tail mice was amplified by PCR followed by sequencing.Incision enzyme FspBI ( BfaI ) identified the genotype of offspring from loop-tail mice intercrossing.Results Heredity test indicated that the loop-tail phenotype was controlled by a single dominant gene not with 100%penetrance but was affected by genetic background.A C-to-T transversion was at the 1345bp in Vangl2 gene of the loop-tail mice.Conclusions The C-to-T transversion introduces a pre-termination codon of amino acids and causes the phenotype of loop-tail phenotype.None homozygous mice were found in the offsprings, suggesting that the homozygous mice are lethal.

Vangl2 and planar cell polarity signaling in cardiac development / 国际儿科学杂志

Planar cell polarity pathway regulates cell polarity and polarized cell movements.Recent studies in mouse models have found mutations in several genes in this pathway and specifically in the Vangl2 gene,which results in abnormalities in cardiac development,suggesting Vangl2 and this pathway play an important role in heart development.This review mainly elucidates the mechanisms regulated by the Vangl2 gene and PCP pathway during outflow tract development and the formation of the coronary vasculature.

Relationship between the expression of Dishevelled2 and Vangl2 and the embryonic neural tube defects induced by excessive retinoic acid in Kunming mice / 解剖学报

ObjectiveTo explore the relationship between the expression of Dishevelled2 and Vangl2 and the embryonic neural tube defects (NTDs) induced by all-trans retinoic acid (RA)in Kunming mouse. Methods Fifty pregnant mice were randomly divided into control and RA-treated groups.RA-treated mice were fed with 30mg/kg RA dissolved with peanut oil on embryo 7.75 days, while the mice of control group were administrated with an equal volume of peanut oil on the same time. Then all the embryos were sampled from pregnant mice at the 4th, 18th, 42nd, 66th and 90th hour after treatment. In situ hybridization and immunohistochemical staining technique were used to detect the expression of Dishevelled2 and Vangl2 in embryonic neural tube. Results The two proteins both existed in the epithelial tissue of the mouse embryonic neural tube and displayed different expression modes at various developmental stages.Compared with the control group, the RA treated group showed a significant decrease (P≤0.05) at the 18th and 42nd hour and a significant increase (P≤0.05) at the 66th hour in Dishevelled2 protein after maternal treatment, and no significant difference was found at the 90th hour. Compared with the control group, the Vangl2 mRNA expression in the RA treated group displayed a significant decrease (P≤0.05) at the 4th and 18th hour and a significant increase (P≤0.05) at the 66th hour after RA treatment, and no difference was found at the 42nd hour. Compared with the control group, the expression of Vangl2 protein in the RA treated group decreased (P≤0.05) at the 18th and 42nd hour, and increased (P≤0.05) at the 90th hour after RA treatment, no difference was found at the 66th hour. Conclusion Excessive RA may interfere with the normal embryonic neural tube closure by regulating the expression of Dishevelled2 and Vangl2.

Expression and its significance of Dishevelled2 and Vangl2 proteins in the developing mouse palate / 解剖学报

Objective To explore the relationship between the expression of Dishevelled2 and Vangl2 proteins and the development of mouse palate. Methods Twenty-four pregnant mice were randomly divided into eight groups, and the mouse embryos were obtained at eight clock of the pregnant day of thirteen(p13d8h), p13d14h,p13d22h,p14d8h,p14d14h,p14d22h,p15d8h and p15d22h respectively, then paraffin sections were made conventionally.The distrubution and dynamic changes of Dishevelled2 and Vangl2 proteins in the embryonic palatal shelves were detected by immunohistochemistry and image analysis. Results It was found that the two kinds of proteins expressed in the epithelium and mesenchyma of the mouse palatal shelves at different development stages. The expression levels of the Dishevelled2,in both of the epithelium and mesenchyme of the palatal shelves, increased first (p13d8h-p13d22h),then decreased rapidly(p13d22h-p14d14h), and then increased again(p14d14h-p15d22h). The expression of Vangl2 protein in the mesenchyma showed a similar trend to that of the Dishevelled2, but there was no obvious regularity in the epithelium. In addition, the expressive levels of both kinds of proteins in the epithelium were significantly higher than those in mesenchyma of the palatal shelves. Conclusion Dishevelled2 and Vangl2 proteins might directly or indirectly take part in the regulation process of mouse palate morphogenesis.