Abstract-Loss-of-function mutations in the human ERG1 potassium channel (hERG1) frequently underlie the long QT2 (LQT2) syndrome. The role of the ERG potassium channel in cardiac development was elaborated in an in vivo model of a homozygous, loss-of-function LQT2 syndrome mutation. The hERG N629D mutation was introduced into the orthologous mouse gene, mERG, by homologous recombination in mouse embryonic stem cells. Intact homozygous embryos showed abrupt cessation of the heart beat. N629D/N629D embryos die in utero by embryonic day 11.5. Their developmental defects include altered looping architecture, poorly developed bulbus cordis, and distorted aortic sac and branchial arches. N629D/N629D myocytes from embryonic day 9.5 embryos manifested complete loss of I Kr function, depolarized resting potential, prolonged action potential duration (LQT), failure to repolarize, and propensity to oscillatory arrhythmias. N629D/N629D myocytes manifest calcium oscillations and increased sarcoplasmic reticulum Ca ϩ2 content. Although the N629D/N629D protein is synthesized, it is mainly located intracellularly, whereas ϩ/ϩ mERG protein is mainly in plasmalemma. N629D/N629D embryos show robust apoptosis in craniofacial regions, particularly in the first branchial arch and, to a lesser extent, in the cardiac outflow tract. Because deletion of Hand2 produces apoptosis, in similar regions and with a similar final developmental phenotype, Hand2 expression was evaluated. Robust decrease in Hand2 expression was observed in the secondary heart field in N629D/N629D embryos. In conclusion, loss of I Kr function in N629D/N629D cardiovascular system leads to defects in cardiac ontogeny in the first branchial arch, outflow tract, and the right ventricle. Key Words: KCNH2 (hERG) Ⅲ knock-in mouse Ⅲ embryo developmental defect T he human ERG gene (hERG/KCNH2) encodes a potassium channel that is important in the late stage of action potential repolarization in heart. Mutations in this gene, which generally reduce plasmalemmal expression of hERG, lead to the long QT2 (LQT2) syndrome in humans. [1][2] Patients with the LQT2 syndrome have a delay in cardiac repolarization that predisposes them to cardiac arrhythmias that can be lethal. 1,2 Mutations in hERG are associated with embryonic lethality and the sudden infant death syndrome. [3][4] Although the LQT2 syndrome generally occurs in individuals heterozygous for the mutant allele, individuals homozygous for the exon 4 duplication manifest embryonic lethality or are rescued in the neonatal period by pacing. 5 Although not widely recognized, mutations of' hERG appear to be associated with structural congenital cardiovascular anomalies including: tetralogy of Fallot, atrial-septal defects, ventricularseptal defects, and patent ductus arteriosus. 6 -9 Mouse ERG (mERG) is the dominant repolarizing current in the mouse embryonic heart. 10 A channel analogous to hERG is expressed in differentiating quail neural crest cells 11 early in development. These data imply a potential role of the ERG potass...
β-Glucan is an important chemical found in cereals, tremendously beneficial to human health. In this study, β-glucan contents in wild and cultivated barley from representative regions worldwide were investigated. Results exhibited that coefficient of variation of β-glucan content of wild and cultivated barley was 24.18% and 13.99%, respectively. The β-glucan contents of studied wild barley accessions were ranged from 3.26% to 7.67% while cultivated barley varieties were ranged from 2.68% to 4.74%. A significant difference of β-glucan content (p ≤ 0.001) was found between wild and cultivated barely. Wild barley showed a higher β-glucan content and variation than cultivated barley. This study gives an idea about elite germplasms for genetic improvement and shed light to trace barley domestication in relation to grain metabolite view.
In higher plants, jasmonate ZIM-domain (JAZ) proteins negatively regulate the biosynthesis of anthocyanins by interacting with bHLH transcription factors. However, it is largely unknown if and how other regulators are involved in this process. In this study, the apple MdJAZ2 protein was characterized in regards to its function in the negative regulation of anthocyanin accumulation and peel coloration. MdJAZ2 was used as a bait to screen a cDNA library using the yeast two-hybrid method. The hypersensitive induced reaction (HIR) proteins, MdHIR2 and MdHIR4, were obtained from this yeast two-hybrid. The ZIM domain of MdJAZ2 and the PHB domain of the MdHIR proteins are necessary for their interactions. The interactions were further verified using an in vitro pull-down assay. Subsequently, immunoblotting assays demonstrated that MdHIR4 enhanced the stability of the MdJAZ2-GUS protein. Finally, a viral vector-based transformation method showed that MdHIR4 inhibited anthocyanin accumulation and fruit coloration in apple by modulating the expression of genes associated with anthocyanin biosynthesis.
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