Hatcher C J, Goldstein M M, Mah C S, Delia C S, Basson C T
Cardiology Division, Department of Medicine and Department of Cell Biology, Weill Medical College of Cornell University, New York, New York 10021, USA.
Dev Dyn. 2000 Sep;219(1):90-5. doi: 10.1002/1097-0177(200009)219:1<90::AID-DVDY1033>3.0.CO;2-L.
Mutations in the TBX5 transcription factor gene cause human cardiac malformation in Holt-Oram syndrome. To identify and localize TBX5 during cardiac morphogenesis, we performed immunohistochemical studies of TBX5 protein cardiac expression during human embryogenesis. Specific antibody to human TBX5 was generated in rabbits with a TBX5 synthetic peptide and affinity purification of antiserum. Anti-TBX5 was used in immunohistochemical analyses of human cardiac tissue. In embryonic and adult heart, TBX5 is expressed throughout the epicardium and in cardiomyocyte nuclei in myocardium of all four cardiac chambers. Endocardial expression of TBX5 is only present in left ventricle. Asymmetric left-sided transmyocardial gradients of TBX5 protein expression were observed in embryonic but not adult hearts. Human cardiac expression of TBX5 protein correlates with the cardiac manifestations of Holt-Oram syndrome. TBX5 transmyocardial protein gradients may contribute to normal patterning of the human heart during embryogenesis.
TBX5转录因子基因突变会导致 Holt-Oram 综合征中的人类心脏畸形。为了在心脏形态发生过程中鉴定和定位 TBX5，我们对人类胚胎发育过程中 TBX5 蛋白在心脏中的表达进行了免疫组织化学研究。用 TBX5 合成肽在兔子体内产生针对人类 TBX5 的特异性抗体，并对抗血清进行亲和纯化。抗 TBX5 用于人类心脏组织的免疫组织化学分析。在胚胎心脏和成年心脏中，TBX5 在整个心外膜以及所有四个心腔心肌的心肌细胞核中均有表达。TBX5 的心内膜表达仅存在于左心室。在胚胎心脏中观察到 TBX5 蛋白表达的不对称左侧跨心肌梯度，而在成年心脏中未观察到。人类心脏中 TBX5 蛋白的表达与 Holt-Oram 综合征的心脏表现相关。TBX5 跨心肌蛋白梯度可能有助于人类心脏在胚胎发育过程中的正常模式形成。
