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A detailed comparison of mouse and human cardiac development.

Krishnan A, Samtani R, Dhanantwari P, Lee E, Yamada S, Shiota K, Donofrio MT, Leatherbury L, Lo CW - Pediatr. Res. (2014)

Bottom Line: Mouse mutants are used to model human congenital cardiovascular disease.We carried out a systematic comparative analysis of mouse and human fetal cardiovascular development.Episcopic fluorescence image capture (EFIC) was performed on 66 wild-type mouse embryos from embryonic day (E) 9.5 to birth; 2-dimensional and 3-dimensional datasets were compared with EFIC and magnetic resonance images from a study of 52 human fetuses (Carnegie stage 13-23).

View Article: PubMed Central - PubMed

Affiliation: 1] Laboratory of Developmental Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland [2] Children's National Heart Institute, Children's National Medical Center, Washington, DC.

ABSTRACT

Background: Mouse mutants are used to model human congenital cardiovascular disease. Few studies exist comparing normal cardiovascular development in mice vs. humans. We carried out a systematic comparative analysis of mouse and human fetal cardiovascular development.

Methods: Episcopic fluorescence image capture (EFIC) was performed on 66 wild-type mouse embryos from embryonic day (E) 9.5 to birth; 2-dimensional and 3-dimensional datasets were compared with EFIC and magnetic resonance images from a study of 52 human fetuses (Carnegie stage 13-23).

Results: Time course of atrial, ventricular, and outflow septation were outlined and followed a similar sequence in both species. Bilateral venae cavae and prominent atrial appendages were seen in the mouse fetus; in human fetuses, atrial appendages were small, and a single right superior vena cava was present. In contrast to humans with separate pulmonary vein orifices, a pulmonary venous confluence with one orifice enters the left atrium in mice.

Conclusion: The cardiac developmental sequences observed in mouse and human fetuses are comparable, with minor differences in atrial and venous morphology. These comparisons of mouse and human cardiac development strongly support that mouse morphogenesis is a good model for human development.

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Related in: MedlinePlus

Comparative Ventricular SeptationA. Mouse heart at E10.5. Scale bar = 250 micrometers.’V’ is ventricle.B. Mouse heart at E12.5. Scale bar = 550 micrometers. ‘RV’ is right ventricle, ‘LV is left ventricle’, and the arrowhead indicates the muscular ventricular septum.C. Mouse heart at E12.5. Scale bar = 450 micrometers. The arrowhead indicates the outlet ventricular septum.D. Mouse heart at E13.5. Scale bar = 600 micrometers.E. Human heart at EGA 6 6/7 weeks (CS 14). Scale bar = 500 micrometers. ‘A’ is atrium, ‘*’ indicates the endocardial cushion, and arrowhead shows the mesenchymal cap.F. Human heart at EGA 8 (CS 18). Scale bar = 1500 micrometers. ‘RA’ is the right atrium, arrowhead indicates the interventricular foramen, and ‘*’ shows the septum primum.G. Human heart at EGA 8 (CS 18). Scale bar = 1500 micrometers. The arrowhead shows the outlet ventricular septum.H. Human heart at EGA 9 1/7 weeks (CS 22). Scale bar = 2000 micrometers. The arrowhead shows the closed interventricular foramen.3A to D illustrate ventricular septation in the mouse and 3E–3H illustrate ventricular septation in the human. Figures 3A and 3E show the cardiac loop in the mouse and human respectively. The arrowhead in 3E illustrates the atrial spine fusing with the inferior cushion (*). The muscular ventricular septum begins to develop at 7 3/7 weeks (CS 16) in the human and E 10.5 in the mouse. Note the rapid progression of the muscular interventricular septum by E12.5 (3B) in the mouse and EGA 8 weeks (CS 18) (3F) in the human. At this stage the outlet septum, indicated by the arrowhead in 3G, is closed (3C mouse, 3G human), but the interventricular foramen (arrowhead in 3F) comprises a small portion of what is clinically termed the membranous and inlet ventricular septum. 3D (mouse, E13.5) and 3H (human, EGA 9 1/7 weeks, CS 22) show closure of the final portion of the interventricular foramen (arrowhead).
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Figure 3: Comparative Ventricular SeptationA. Mouse heart at E10.5. Scale bar = 250 micrometers.’V’ is ventricle.B. Mouse heart at E12.5. Scale bar = 550 micrometers. ‘RV’ is right ventricle, ‘LV is left ventricle’, and the arrowhead indicates the muscular ventricular septum.C. Mouse heart at E12.5. Scale bar = 450 micrometers. The arrowhead indicates the outlet ventricular septum.D. Mouse heart at E13.5. Scale bar = 600 micrometers.E. Human heart at EGA 6 6/7 weeks (CS 14). Scale bar = 500 micrometers. ‘A’ is atrium, ‘*’ indicates the endocardial cushion, and arrowhead shows the mesenchymal cap.F. Human heart at EGA 8 (CS 18). Scale bar = 1500 micrometers. ‘RA’ is the right atrium, arrowhead indicates the interventricular foramen, and ‘*’ shows the septum primum.G. Human heart at EGA 8 (CS 18). Scale bar = 1500 micrometers. The arrowhead shows the outlet ventricular septum.H. Human heart at EGA 9 1/7 weeks (CS 22). Scale bar = 2000 micrometers. The arrowhead shows the closed interventricular foramen.3A to D illustrate ventricular septation in the mouse and 3E–3H illustrate ventricular septation in the human. Figures 3A and 3E show the cardiac loop in the mouse and human respectively. The arrowhead in 3E illustrates the atrial spine fusing with the inferior cushion (*). The muscular ventricular septum begins to develop at 7 3/7 weeks (CS 16) in the human and E 10.5 in the mouse. Note the rapid progression of the muscular interventricular septum by E12.5 (3B) in the mouse and EGA 8 weeks (CS 18) (3F) in the human. At this stage the outlet septum, indicated by the arrowhead in 3G, is closed (3C mouse, 3G human), but the interventricular foramen (arrowhead in 3F) comprises a small portion of what is clinically termed the membranous and inlet ventricular septum. 3D (mouse, E13.5) and 3H (human, EGA 9 1/7 weeks, CS 22) show closure of the final portion of the interventricular foramen (arrowhead).

Mentions: Atrial septation in mice occurred over E10.5–E13.5; in human fetuses, this was comparable to (Carnegie stage) CS 14–18 or estimated gestational age (EGA) 6 6/7 – 8 weeks. The primary atrial septum, a left sided structure, develops from the superior aspect of the common atrium between the systemic and pulmonary vein orifices. It was first noted at E10.5 in the mouse and CS 14 (6 6/7 weeks EGA) in the human (Figure 3E). At the inferior end of the primary septum is a mesenchymal cap, which could be seen merging with the superior endocardial cushion, and indicated by the arrowhead in Figure 3E. The vestibular spine, a mesenchymal structure, begins to grow from the posterior aspect of mediastinum, rightward of the pulmonary vein orifice. The vestibular spine was present at stage E11.5 in the mouse. At this stage, septum secundum was noted as well. The ostium primum had not yet closed at this stage. Image quality of the atrial septum from the E10.5 and E11.5 mouse specimens was not of high enough quality for publication in the figures, but these structures are illustrated in the human in Figure 3E. The mesenchymal cap, vestibular spine, and superior and inferior cushions eventually fuse, effectively eliminating the ostium primum (Figures 3A and 3E). The mesenchymal tissue becomes muscularized (9), and is the structure known postnatally as septum primum. A second opening, the ostium secundum, develops from dissolution of the superior aspect of the primary atrial septum and is termed the foramen ovale by fetal echocardiographers. Septum secundum forms from a tissue fold from the posterior portion of the atrium to right of the pulmonary vein orifice (9).


A detailed comparison of mouse and human cardiac development.

Krishnan A, Samtani R, Dhanantwari P, Lee E, Yamada S, Shiota K, Donofrio MT, Leatherbury L, Lo CW - Pediatr. Res. (2014)

Comparative Ventricular SeptationA. Mouse heart at E10.5. Scale bar = 250 micrometers.’V’ is ventricle.B. Mouse heart at E12.5. Scale bar = 550 micrometers. ‘RV’ is right ventricle, ‘LV is left ventricle’, and the arrowhead indicates the muscular ventricular septum.C. Mouse heart at E12.5. Scale bar = 450 micrometers. The arrowhead indicates the outlet ventricular septum.D. Mouse heart at E13.5. Scale bar = 600 micrometers.E. Human heart at EGA 6 6/7 weeks (CS 14). Scale bar = 500 micrometers. ‘A’ is atrium, ‘*’ indicates the endocardial cushion, and arrowhead shows the mesenchymal cap.F. Human heart at EGA 8 (CS 18). Scale bar = 1500 micrometers. ‘RA’ is the right atrium, arrowhead indicates the interventricular foramen, and ‘*’ shows the septum primum.G. Human heart at EGA 8 (CS 18). Scale bar = 1500 micrometers. The arrowhead shows the outlet ventricular septum.H. Human heart at EGA 9 1/7 weeks (CS 22). Scale bar = 2000 micrometers. The arrowhead shows the closed interventricular foramen.3A to D illustrate ventricular septation in the mouse and 3E–3H illustrate ventricular septation in the human. Figures 3A and 3E show the cardiac loop in the mouse and human respectively. The arrowhead in 3E illustrates the atrial spine fusing with the inferior cushion (*). The muscular ventricular septum begins to develop at 7 3/7 weeks (CS 16) in the human and E 10.5 in the mouse. Note the rapid progression of the muscular interventricular septum by E12.5 (3B) in the mouse and EGA 8 weeks (CS 18) (3F) in the human. At this stage the outlet septum, indicated by the arrowhead in 3G, is closed (3C mouse, 3G human), but the interventricular foramen (arrowhead in 3F) comprises a small portion of what is clinically termed the membranous and inlet ventricular septum. 3D (mouse, E13.5) and 3H (human, EGA 9 1/7 weeks, CS 22) show closure of the final portion of the interventricular foramen (arrowhead).
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Figure 3: Comparative Ventricular SeptationA. Mouse heart at E10.5. Scale bar = 250 micrometers.’V’ is ventricle.B. Mouse heart at E12.5. Scale bar = 550 micrometers. ‘RV’ is right ventricle, ‘LV is left ventricle’, and the arrowhead indicates the muscular ventricular septum.C. Mouse heart at E12.5. Scale bar = 450 micrometers. The arrowhead indicates the outlet ventricular septum.D. Mouse heart at E13.5. Scale bar = 600 micrometers.E. Human heart at EGA 6 6/7 weeks (CS 14). Scale bar = 500 micrometers. ‘A’ is atrium, ‘*’ indicates the endocardial cushion, and arrowhead shows the mesenchymal cap.F. Human heart at EGA 8 (CS 18). Scale bar = 1500 micrometers. ‘RA’ is the right atrium, arrowhead indicates the interventricular foramen, and ‘*’ shows the septum primum.G. Human heart at EGA 8 (CS 18). Scale bar = 1500 micrometers. The arrowhead shows the outlet ventricular septum.H. Human heart at EGA 9 1/7 weeks (CS 22). Scale bar = 2000 micrometers. The arrowhead shows the closed interventricular foramen.3A to D illustrate ventricular septation in the mouse and 3E–3H illustrate ventricular septation in the human. Figures 3A and 3E show the cardiac loop in the mouse and human respectively. The arrowhead in 3E illustrates the atrial spine fusing with the inferior cushion (*). The muscular ventricular septum begins to develop at 7 3/7 weeks (CS 16) in the human and E 10.5 in the mouse. Note the rapid progression of the muscular interventricular septum by E12.5 (3B) in the mouse and EGA 8 weeks (CS 18) (3F) in the human. At this stage the outlet septum, indicated by the arrowhead in 3G, is closed (3C mouse, 3G human), but the interventricular foramen (arrowhead in 3F) comprises a small portion of what is clinically termed the membranous and inlet ventricular septum. 3D (mouse, E13.5) and 3H (human, EGA 9 1/7 weeks, CS 22) show closure of the final portion of the interventricular foramen (arrowhead).
Mentions: Atrial septation in mice occurred over E10.5–E13.5; in human fetuses, this was comparable to (Carnegie stage) CS 14–18 or estimated gestational age (EGA) 6 6/7 – 8 weeks. The primary atrial septum, a left sided structure, develops from the superior aspect of the common atrium between the systemic and pulmonary vein orifices. It was first noted at E10.5 in the mouse and CS 14 (6 6/7 weeks EGA) in the human (Figure 3E). At the inferior end of the primary septum is a mesenchymal cap, which could be seen merging with the superior endocardial cushion, and indicated by the arrowhead in Figure 3E. The vestibular spine, a mesenchymal structure, begins to grow from the posterior aspect of mediastinum, rightward of the pulmonary vein orifice. The vestibular spine was present at stage E11.5 in the mouse. At this stage, septum secundum was noted as well. The ostium primum had not yet closed at this stage. Image quality of the atrial septum from the E10.5 and E11.5 mouse specimens was not of high enough quality for publication in the figures, but these structures are illustrated in the human in Figure 3E. The mesenchymal cap, vestibular spine, and superior and inferior cushions eventually fuse, effectively eliminating the ostium primum (Figures 3A and 3E). The mesenchymal tissue becomes muscularized (9), and is the structure known postnatally as septum primum. A second opening, the ostium secundum, develops from dissolution of the superior aspect of the primary atrial septum and is termed the foramen ovale by fetal echocardiographers. Septum secundum forms from a tissue fold from the posterior portion of the atrium to right of the pulmonary vein orifice (9).

Bottom Line: Mouse mutants are used to model human congenital cardiovascular disease.We carried out a systematic comparative analysis of mouse and human fetal cardiovascular development.Episcopic fluorescence image capture (EFIC) was performed on 66 wild-type mouse embryos from embryonic day (E) 9.5 to birth; 2-dimensional and 3-dimensional datasets were compared with EFIC and magnetic resonance images from a study of 52 human fetuses (Carnegie stage 13-23).

View Article: PubMed Central - PubMed

Affiliation: 1] Laboratory of Developmental Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland [2] Children's National Heart Institute, Children's National Medical Center, Washington, DC.

ABSTRACT

Background: Mouse mutants are used to model human congenital cardiovascular disease. Few studies exist comparing normal cardiovascular development in mice vs. humans. We carried out a systematic comparative analysis of mouse and human fetal cardiovascular development.

Methods: Episcopic fluorescence image capture (EFIC) was performed on 66 wild-type mouse embryos from embryonic day (E) 9.5 to birth; 2-dimensional and 3-dimensional datasets were compared with EFIC and magnetic resonance images from a study of 52 human fetuses (Carnegie stage 13-23).

Results: Time course of atrial, ventricular, and outflow septation were outlined and followed a similar sequence in both species. Bilateral venae cavae and prominent atrial appendages were seen in the mouse fetus; in human fetuses, atrial appendages were small, and a single right superior vena cava was present. In contrast to humans with separate pulmonary vein orifices, a pulmonary venous confluence with one orifice enters the left atrium in mice.

Conclusion: The cardiac developmental sequences observed in mouse and human fetuses are comparable, with minor differences in atrial and venous morphology. These comparisons of mouse and human cardiac development strongly support that mouse morphogenesis is a good model for human development.

Show MeSH
Related in: MedlinePlus