BMPR IA downstream genes related to VSD.
Cardiac-specific deletion of the receptor IA of bone morphogenetic protein (BMP) (ALK3) by Cre recombinase driven under the [alpha]-MHC promoter is lethal in mid-gestation with defects in the interventricular septum [ventricular septum defect (VSD)]. Analysis of expression of the ALK3 downstream genes is important to identify the signaling pathway for interventricular septum development. The mRNA expression level of a control group was compared with that of a test group. ALK3 downstream genes were screened using polymerase chain reaction (PCR)-select cDNA subtraction and microarray. It was found that the mice with an ALK3 knockout gene produced a VSD. The expression of some genes such as platelet-activating factor acetylhydrolase (PAF) and Pax-8 was down-regulated in the test group. Pax-8 gene expression was down-regulated by 7.1 times in the test group and expressed specifically in the 11.5-d embryonic (E11.5) heart. Furthermore, the expression of the protein-tyrosine kinase of the focal adhesion kinase subfamily (PTK) and [beta] subtype protein 14-3-3 was up-regulated in the test group. PTK gene expression was up-regulated by 3.7 times in the test group. These data provided support that the ALK3 gene plays an important role during heart development. The PAF and Pax-8 genes could be important ALK3 downstream genes in the BMP signaling pathway during interventricular septum development. PTK and [beta] subtype protein 14-3-3 might be regulatory factors in this pathway.
Yang
Deye
D
Department of Cardiology, The First Affiliated Hospital, Institute ofor Cardiovascular Biology and Gene, Wenzhou Medical College, Wenzhou 325000, PR China. deyeyang@hotmail.com
Zhang
Jiayin
J
Chen
Changxi
C
Xie
Min
M
Sperling
Silke
S
Fang
Fei
F
Chen
Binxin
B
Li
Xiaowang
X
Zhang
Huaiqin
H
D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006345:Heart Septal Defects, Ventricular / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D006346:Heart Septum / Q000196:embryology; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024510:Muscle Development / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D012333:RNA, Messenger; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I