septumdownstreamactivatingkinaseembryonicsubfamilysubtractionpromotermorphogeneticsubtype
摘要：<正>Cardiac-specific deletion of the receptor IA of bone morphogenetic protein, ALK3, by Cre recombinase driven under the a-MHC promoter is lethal in mid-gestation with defects in the interventricular septum. Analysis of expression of the ALK3 downstream genes is important to identify the signaling pathway for interventricular septum development. The model mice with ALK3 gene knockout via a-MHC-Cre/lox P system were bred. The mRNA expression level of control group was compared with that of test group. ALK3 downstream genes were screened using PCR-select cDNA subtraction and microarray. It was found that the mice with ALK3 gene knockout produced heart defects involving the interventricular septum. The expression of some genes such as platelet-activating factor acetylhydrolase and the transcription factor Pax-8 etc was downregulated in the test group. The box protein Pax-8 gene expression was downregulated by 7.1 times in the test group and expressed specifically in the embryonic heart (11.5 days). Furthermore, the expression of the Protein Tyrosine Kinase of Focal Adhesion Kinase subfamily (PTK) and beta subtype protein 14-3-3 was upregulated in the a-MHC-Cre+/-ALK3 F/-mice. PTK gene expression was up-regulated by 3.7 times in the test group. These data provided support that ALK3 gene played an important role during heart development. The platelet-activating factor acetylhydrolase and Pax-8 genes could be important ALK3 downstream genes in the BMP signaling pathway during interventncular septum development. PTK and beta subtype protein 14-3-3 might be regulatory factors in this pathway.
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