ZFIN ID: ZDB-FIG-190726-11
Silbernagel et al., 2018 - The VAMP-associated protein VAPB is required for cardiac and neuronal pacemaker channel function. FASEB journal : official publication of the Federation of American Societies for Experimental Biology   32(11):6159-6173 Full text @ FASEB J.
ADDITIONAL FIGURES
PHENOTYPE:
Fish:
Knockdown Reagents:
Observed In:
Stage: Protruding-mouth

Figure 5

Bradycardia in knock-down zebrafish embryos and VAPB−/− mice. A) Zebrafish embryos at 72 hpf. Control-injected and MO-injected embryos against VAPA (MOVAPA) or VAPB (MOVAPB) exhibit no significant abnormalities (left), particularly no structural heart defects (right). Note a light cardiac edema in MOVAPB and a strong edema in MOVAPA. B) Heart rate in beats per minute (bpm) of control and MOVAPA, MOVAPB, or MOVAPA/B injected zebrafish embryos at 72 hpf. C) Representative examples of calcium transients (relative fluorescence intensity) in the cardiac atrium (black) and cardiac ventricle (gray) of control-injected zebrafish at 72 hpf, displaying a regular atrio-ventricular propagation of excitation from atrium to ventricle in a 1:1-ratio. D, E), Representative calcium transients recorded in MOVAPA/B double knock-down morphants, illustrating strongly reduced heart rates with variable frequency. F) Representative example of atrial and ventricular calcium measurements from a MOVAPA/B morphant with a 2:1 atrio-ventricular block, in which only every second atrial excitation leads to a ventricular excitation. Data were obtained from 3 independent batches of injections (AF). G) Heart rate in beats per minute (bpm) of VAPB−/− mice compared with wild-type littermates (control), analyzed by using tail-cuff measurements. H) Representative surface ECG recordings of VAPB−/− mice and their wild-type littermates (control). ECGs of VAPB−/− mice show bradycardia and an increased T-wave amplitude. IN) Analyses of the ECG parameters of VAPB−/− mice. I) Heart rate in beats per minute (bpm). J) PQ interval (PQ) duration. K) QRS complex (QRS) duration. L) Frequency corrected QT interval (QTc). M) Frequency-corrected Tpeak to Tend duration (Tp-Tec). N) T-wave amplitude (JTp). Scale bars: 500 µm (A); 500 ms (CF), and 100 ms (H). All data are presented as means ± sem. The number of animals (n) is indicated in the respective bar graphs. N.s., not significant. *P < 0.05, **P < 0.01, ***P < 0.001 [Student’s t test (G, H, J–N) or Welch’s t test (B, I)].

Gene Expression Details No data available
Antibody Labeling Details No data available
Phenotype Details
Fish Conditions Stage Phenotype
TU + MO1-vapa standard conditions Protruding-mouth cardiac conduction process quality, normal
Protruding-mouth heart contraction decreased rate, abnormal
Protruding-mouth pericardium edematous, abnormal
TU + MO1-vapa + MO1-vapb standard conditions Protruding-mouth cardiac conduction disrupted, abnormal
Protruding-mouth heart contraction decreased rate, exacerbated
Protruding-mouth heart contraction frequency, abnormal
Protruding-mouth heart contraction rhythm quality, abnormal
TU + MO1-vapb standard conditions Protruding-mouth cardiac conduction process quality, normal
Protruding-mouth heart contraction decreased rate, abnormal
Protruding-mouth pericardium edematous, abnormal
Acknowledgments:
ZFIN wishes to thank the journal FASEB journal : official publication of the Federation of American Societies for Experimental Biology for permission to reproduce figures from this article. Please note that this material may be protected by copyright. Full text @ FASEB J.