mortality/aging
• fewer than expected ganciclovir-treated mice are present at E12.5 due to death associated with cardiac defects
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cardiovascular system
• in mice treated with ganciclovir
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• 73% of ganciclovir-treated mice with truncus arteriosis exhibit type 4A with a small ascending aortic component, a large ductus arteriosus, and underdevelopment of the arch that is associated with interrupted aortic arch
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• 10% of ganciclovir-treated mice with interrupted aortic arch exhibit type B interruptions between the take off of the left common carotid artery and the left subclavian artery
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• 90% of ganciclovir-treated mice with interrupted aortic arch exhibit type C interruptions between the brachiocephalic artery and the left common carotid artery
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• in mice treated with ganciclovir
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• male mice treated with two injections of ganciclovir at E7.5 and E8.5 exhibit truncus arteriosis and aortic arch anomalies while 100% of mice treated with ganciclovir injections at E7.5, E8.5 and E9.5 exhibit truncus arteriosis and aortic arch defects
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• at E9.5, ganciclovir-treated mice the outflow tract is underdeveloped, assumes a more dorsal position compared to in wild-type mice, and exhibits elongation and looping defects
• at E10.5, outflow tract cushion mesenchyme cellularity is reduced in mice treated with ganciclovir
• the outflow tract fails to expand as in wild-type mice with 7 of 12 mice exhibiting hypoblastic aortic side and 5 of 12 mice with hypoplastic pulmonary side
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• at E13.5, ganciclovir-treated mice exhibit ventricular septum defects with or without truncus arteriosus
• 73% of ganciclovir-treated mice with truncus arteriosis exhibit type 4A (small ascending aortic component, a large ductus arteriosus, and underdevelopment of the arch that is associated with interrupted aortic arch) while 10% exhibit type A2 (absent ductus arteriosis and a large ascending aorta and aortic arch components), and 17% exhibit type A1 (partially formed aorticopulmonary septum separating the common trunk into aortic and pulmonary components distally)
• 6 of 7 ganciclovir-treated mice exhibit the absence of the ductus arteriosus
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• at E13.5, some ganciclovir-treated mice exhibit ventricular septum defects with double outlet right ventricle that is associated with a lack of semilunar valve to the artrioventricular valve fibrous continuity
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• at E13.5, ganciclovir-treated mice exhibit ventricular septum defects with or without dextroposition of the aorta, truncus arteriosus and double outlet right ventricle
• 29% of ganciclovir-treated mice exhibit side-by-side great arteries while 71% exhibit an aorta that is posterior and to the right of the pulmonary artery
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• in ganciclovir-treated mice
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• at E13.5, ganciclovir-treated mice exhibit ventricular septum defects with or without dextroposition of the aorta, truncus arteriosus and double outlet right ventricle that is either uncommitted or subaortic
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• in ganciclovir-treated mice at E10.5
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• at E12.5-15.5, 3 of 12 ganciclovir-treated mice exhibit a hypoplastic fourth cusp on the truncal valve
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• at E14.5, ganciclovir-treated mice exhibit a fibrous continuity between the aortic valve and the mitral valve that connects to the left ventricle
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• at E14.5, ganciclovir-treated mice exhibit a fibrous continuity between the aortic valve and the mitral valve that connects to the left ventricle
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• at E9.5, ganciclovir-treated mice the right ventricle is underdeveloped and more dorsally located compared to in wild-type mice
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• 29% of ganciclovir-treated mice with double outlet right ventricles exhibit stenosis or hypoplasia of the pulmonary outflow tract
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• 29% of ganciclovir-treated mice with double outlet right ventricles exhibit stenosis or hypoplasia of the pulmonary outflow tract and pulmonary valve
• 3 ganciclovir-treated mice with pulmonary stenosis exhibit an aortic valve positioned posterior and to the right of the pulmonary valve reminiscent of cases of tetralogy of Fallot
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• in ganciclovir-treated mice at E10.5
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• ganciclovir-treated mice that die by E12.5 exhibit signs of congestive heart failure such as generalized edema, enlarged heart, pericardial effusion and small gestational size
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embryo
• at E10.5, mice treated with ganciclovir exhibit little pharyngeal arch mesenchyme unlike wild-type mice
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• at E10.5, ganciclovir-treated mice are smaller than wild-type mice
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• when mice are treated with a single injection of ganciclovir at E7.5 neural crest cells of the cephalic portion of the neural tube and the first pharyngeal arch, but not cardiac neural crest cells, are ablated
• when mice are treated with a single injection of ganciclovir at E8.5 neural crest cells at all axial levels are ablated whereas a double injection of ganciclovir at E8.5 results in ablation of neural crest cells along the full length of the neural tube and those that have migrated to the first three pharyngeal arches
• however, when mice are treated with a single injection of ganciclovir at E7.0 neural crest cells develop normally
• male mice injected with a single dose of ganciclovir at E7.5 and E8.5 exhibit more extensive neural crest cells ablation than female mice
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nervous system
• when mice are treated with a single injection of ganciclovir at E7.5 neural crest cells of the cephalic portion of the neural tube and the first pharyngeal arch, but not cardiac neural crest cells, are ablated
• when mice are treated with a single injection of ganciclovir at E8.5 neural crest cells at all axial levels are ablated whereas a double injection of ganciclovir at E8.5 results in ablation of neural crest cells along the full length of the neural tube and those that have migrated to the first three pharyngeal arches
• however, when mice are treated with a single injection of ganciclovir at E7.0 neural crest cells develop normally
• male mice injected with a single dose of ganciclovir at E7.5 and E8.5 exhibit more extensive neural crest cells ablation than female mice
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craniofacial
• at E9.5, male mice injected with a single dose of ganciclovir at E7.5 and E8.5 exhibit more severe craniofacial defects than females
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• at E10.5, mice treated with ganciclovir exhibit little pharyngeal arch mesenchyme unlike wild-type mice
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homeostasis/metabolism
• in ganciclovir-treated mice at E10.5
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growth/size/body
• in ganciclovir-treated mice at E10.5
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• at E10.5, mice treated with ganciclovir exhibit little pharyngeal arch mesenchyme unlike wild-type mice
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• at E10.5, ganciclovir-treated mice are smaller than wild-type mice
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