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Premature death following acute genetic ablation of p53 and Mdm2 is elicited by drastic bradycardia followed by asystole. (A) Expression levels of hypertrophic and sarcomeric marker genes: atrial natriuretic factor (ANP), brain natriuretic factor (BNP), α-myosin heavy chain (α-MHC), β-myosin heavy chain (β-MHC), phospholamban (Pln), ryanodine receptor (Ryr2), troponin C (Tnnc1), tropomyosin (Tpm1), and titin (Ttn) as analyzed by RT-qPCR in DKO (8d), Mdm2KO (14d) and p53KO (3 months) mice post-Tam compared with vehicle-injected controls. Data are represented as the mRNA expression ratio change compared with vehicle-injected controls for each primer using the ΔΔCt method ± s.e.m, n = 4. A significant difference between the mean normalized delta Ct values versus vehicle-injected control is indicated by *P ≤ 0.05 and **P ≤ 0.01, determined by the Student's T-test. (B) Kaplan-Meier survival curves of conditional DKO, Mdm2KO and p53KO mice post-Tam. n = 10. (C) Transmission electron micrographs of left ventricular samples from vehicle-injected control (left) and DKO (right) mice. The absence of the M-line (white arrow) and the diffuse nature of Z-line (black arrow) indicate a potential change in the alignment of the actin-myosin filaments within the sarcomere. (D-G) Tam-injected DKO mice develop varying degrees of heart block and bradycardia as determined by telemetric <t>electrocardiography.</t> (D) DKO mice post-Tam develop sinus arrest, (E) bradycardia with loss of the circadian rhythm, (F) atrio-ventricular block, and (G) ventricular tachycardia. U, voltage. mV, millivolt. sec, seconds. One representative result of 4 independent experiments is shown. Averaged heart rate in beats per minute. One representative result of 4 independent experiments is shown.
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Premature death following acute genetic ablation of p53 and Mdm2 is elicited by drastic bradycardia followed by asystole. (A) Expression levels of hypertrophic and sarcomeric marker genes: atrial natriuretic factor (ANP), brain natriuretic factor (BNP), α-myosin heavy chain (α-MHC), β-myosin heavy chain (β-MHC), phospholamban (Pln), ryanodine receptor (Ryr2), troponin C (Tnnc1), tropomyosin (Tpm1), and titin (Ttn) as analyzed by RT-qPCR in DKO (8d), Mdm2KO (14d) and p53KO (3 months) mice post-Tam compared with vehicle-injected controls. Data are represented as the mRNA expression ratio change compared with vehicle-injected controls for each primer using the ΔΔCt method ± s.e.m, n = 4. A significant difference between the mean normalized delta Ct values versus vehicle-injected control is indicated by *P ≤ 0.05 and **P ≤ 0.01, determined by the Student's T-test. (B) Kaplan-Meier survival curves of conditional DKO, Mdm2KO and p53KO mice post-Tam. n = 10. (C) Transmission electron micrographs of left ventricular samples from vehicle-injected control (left) and DKO (right) mice. The absence of the M-line (white arrow) and the diffuse nature of Z-line (black arrow) indicate a potential change in the alignment of the actin-myosin filaments within the sarcomere. (D-G) Tam-injected DKO mice develop varying degrees of heart block and bradycardia as determined by telemetric <t>electrocardiography.</t> (D) DKO mice post-Tam develop sinus arrest, (E) bradycardia with loss of the circadian rhythm, (F) atrio-ventricular block, and (G) ventricular tachycardia. U, voltage. mV, millivolt. sec, seconds. One representative result of 4 independent experiments is shown. Averaged heart rate in beats per minute. One representative result of 4 independent experiments is shown.
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Premature death following acute genetic ablation of p53 and Mdm2 is elicited by drastic bradycardia followed by asystole. (A) Expression levels of hypertrophic and sarcomeric marker genes: atrial natriuretic factor (ANP), brain natriuretic factor (BNP), α-myosin heavy chain (α-MHC), β-myosin heavy chain (β-MHC), phospholamban (Pln), ryanodine receptor (Ryr2), troponin C (Tnnc1), tropomyosin (Tpm1), and titin (Ttn) as analyzed by RT-qPCR in DKO (8d), Mdm2KO (14d) and p53KO (3 months) mice post-Tam compared with vehicle-injected controls. Data are represented as the mRNA expression ratio change compared with vehicle-injected controls for each primer using the ΔΔCt method ± s.e.m, n = 4. A significant difference between the mean normalized delta Ct values versus vehicle-injected control is indicated by *P ≤ 0.05 and **P ≤ 0.01, determined by the Student's T-test. (B) Kaplan-Meier survival curves of conditional DKO, Mdm2KO and p53KO mice post-Tam. n = 10. (C) Transmission electron micrographs of left ventricular samples from vehicle-injected control (left) and DKO (right) mice. The absence of the M-line (white arrow) and the diffuse nature of Z-line (black arrow) indicate a potential change in the alignment of the actin-myosin filaments within the sarcomere. (D-G) Tam-injected DKO mice develop varying degrees of heart block and bradycardia as determined by telemetric <t>electrocardiography.</t> (D) DKO mice post-Tam develop sinus arrest, (E) bradycardia with loss of the circadian rhythm, (F) atrio-ventricular block, and (G) ventricular tachycardia. U, voltage. mV, millivolt. sec, seconds. One representative result of 4 independent experiments is shown. Averaged heart rate in beats per minute. One representative result of 4 independent experiments is shown.
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Premature death following acute genetic ablation of p53 and Mdm2 is elicited by drastic bradycardia followed by asystole. (A) Expression levels of hypertrophic and sarcomeric marker genes: atrial natriuretic factor (ANP), brain natriuretic factor (BNP), α-myosin heavy chain (α-MHC), β-myosin heavy chain (β-MHC), phospholamban (Pln), ryanodine receptor (Ryr2), troponin C (Tnnc1), tropomyosin (Tpm1), and titin (Ttn) as analyzed by RT-qPCR in DKO (8d), Mdm2KO (14d) and p53KO (3 months) mice post-Tam compared with vehicle-injected controls. Data are represented as the mRNA expression ratio change compared with vehicle-injected controls for each primer using the ΔΔCt method ± s.e.m, n = 4. A significant difference between the mean normalized delta Ct values versus vehicle-injected control is indicated by *P ≤ 0.05 and **P ≤ 0.01, determined by the Student's T-test. (B) Kaplan-Meier survival curves of conditional DKO, Mdm2KO and p53KO mice post-Tam. n = 10. (C) Transmission electron micrographs of left ventricular samples from vehicle-injected control (left) and DKO (right) mice. The absence of the M-line (white arrow) and the diffuse nature of Z-line (black arrow) indicate a potential change in the alignment of the actin-myosin filaments within the sarcomere. (D-G) Tam-injected DKO mice develop varying degrees of heart block and bradycardia as determined by telemetric <t>electrocardiography.</t> (D) DKO mice post-Tam develop sinus arrest, (E) bradycardia with loss of the circadian rhythm, (F) atrio-ventricular block, and (G) ventricular tachycardia. U, voltage. mV, millivolt. sec, seconds. One representative result of 4 independent experiments is shown. Averaged heart rate in beats per minute. One representative result of 4 independent experiments is shown.
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Premature death following acute genetic ablation of p53 and Mdm2 is elicited by drastic bradycardia followed by asystole. (A) Expression levels of hypertrophic and sarcomeric marker genes: atrial natriuretic factor (ANP), brain natriuretic factor (BNP), α-myosin heavy chain (α-MHC), β-myosin heavy chain (β-MHC), phospholamban (Pln), ryanodine receptor (Ryr2), troponin C (Tnnc1), tropomyosin (Tpm1), and titin (Ttn) as analyzed by RT-qPCR in DKO (8d), Mdm2KO (14d) and p53KO (3 months) mice post-Tam compared with vehicle-injected controls. Data are represented as the mRNA expression ratio change compared with vehicle-injected controls for each primer using the ΔΔCt method ± s.e.m, n = 4. A significant difference between the mean normalized delta Ct values versus vehicle-injected control is indicated by *P ≤ 0.05 and **P ≤ 0.01, determined by the Student's T-test. (B) Kaplan-Meier survival curves of conditional DKO, Mdm2KO and p53KO mice post-Tam. n = 10. (C) Transmission electron micrographs of left ventricular samples from vehicle-injected control (left) and DKO (right) mice. The absence of the M-line (white arrow) and the diffuse nature of Z-line (black arrow) indicate a potential change in the alignment of the actin-myosin filaments within the sarcomere. (D-G) Tam-injected DKO mice develop varying degrees of heart block and bradycardia as determined by telemetric electrocardiography. (D) DKO mice post-Tam develop sinus arrest, (E) bradycardia with loss of the circadian rhythm, (F) atrio-ventricular block, and (G) ventricular tachycardia. U, voltage. mV, millivolt. sec, seconds. One representative result of 4 independent experiments is shown. Averaged heart rate in beats per minute. One representative result of 4 independent experiments is shown.

Journal: Cell Cycle

Article Title: p53 and Mdm2 act synergistically to maintain cardiac homeostasis and mediate cardiomyocyte cell cycle arrest through a network of microRNAs

doi: 10.1080/15384101.2017.1346758

Figure Lengend Snippet: Premature death following acute genetic ablation of p53 and Mdm2 is elicited by drastic bradycardia followed by asystole. (A) Expression levels of hypertrophic and sarcomeric marker genes: atrial natriuretic factor (ANP), brain natriuretic factor (BNP), α-myosin heavy chain (α-MHC), β-myosin heavy chain (β-MHC), phospholamban (Pln), ryanodine receptor (Ryr2), troponin C (Tnnc1), tropomyosin (Tpm1), and titin (Ttn) as analyzed by RT-qPCR in DKO (8d), Mdm2KO (14d) and p53KO (3 months) mice post-Tam compared with vehicle-injected controls. Data are represented as the mRNA expression ratio change compared with vehicle-injected controls for each primer using the ΔΔCt method ± s.e.m, n = 4. A significant difference between the mean normalized delta Ct values versus vehicle-injected control is indicated by *P ≤ 0.05 and **P ≤ 0.01, determined by the Student's T-test. (B) Kaplan-Meier survival curves of conditional DKO, Mdm2KO and p53KO mice post-Tam. n = 10. (C) Transmission electron micrographs of left ventricular samples from vehicle-injected control (left) and DKO (right) mice. The absence of the M-line (white arrow) and the diffuse nature of Z-line (black arrow) indicate a potential change in the alignment of the actin-myosin filaments within the sarcomere. (D-G) Tam-injected DKO mice develop varying degrees of heart block and bradycardia as determined by telemetric electrocardiography. (D) DKO mice post-Tam develop sinus arrest, (E) bradycardia with loss of the circadian rhythm, (F) atrio-ventricular block, and (G) ventricular tachycardia. U, voltage. mV, millivolt. sec, seconds. One representative result of 4 independent experiments is shown. Averaged heart rate in beats per minute. One representative result of 4 independent experiments is shown.

Article Snippet: Mice were anaesthetized (1% isoflurane inhalation) and implanted with radiofrequency electrocardiogram (ECG) transmitters (DSI PhysioTel Transmitter EA-F20; Data Sciences International, St. Paul, MN 55112 USA).

Techniques: Expressing, Marker, Quantitative RT-PCR, Injection, Transmission Assay, Blocking Assay