Phenotypes associated with this allele
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7tm2a(EUCOMM)Wtsi mutation
(1 available);
any
Chd7 mutation
(136 available)
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mortality/aging
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• only 2 homozygous embryos were found at E14.5, suggesting most die mid-gestation
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7tm2a(EUCOMM)Wtsi mutation
(1 available);
any
Chd7 mutation
(136 available)
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embryo
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• no apparent gross abnormality at E9.5 but fully penetrant growth arrest at E10.5
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mortality/aging
cellular
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• significantly reduced active epigenetic state of Nkx2-5 enhancers in E10.0 hearts
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cardiovascular system
N |
• no myocardial defect at E9.5
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• at E10.5, mutant displays hypocellular myocardial wall
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• fewer mesenchymal cells present in AV cushions at E9.5
• at E10.5, mutant displays hypocellular AV cushions
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muscle
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• at E10.5, mutant displays hypocellular myocardial wall
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7tm2a(EUCOMM)Wtsi mutation
(1 available);
any
Chd7 mutation
(136 available)
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Data Sources
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behavior/neurological
skeleton
growth/size/body
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IMPC - WTSI
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7tm2a(EUCOMM)Wtsi mutation
(1 available);
any
Chd7 mutation
(136 available)
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nervous system
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• absence of midline crossing resulting in dysgenesis of the corpus callosum in 3 of 3 mice
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• increase of 100% on average on both sides of the brain
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behavior/neurological
N |
• no increase in locomotor activity during a modified SHIRPA or in the open field unlike mice heterozygous for Chd7Whi
• no change in heat sensitivity compared to controls
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• show a trend toward reduced response
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• less severe than in mice heterozygous for Chd7Whi
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hematopoietic system
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• percentage tends to be decreased but is not statistically significant
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vision/eye
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• abnormal pupil position or shape in 5 of 14 mice
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• opaque lenses in mice with normal pupils only
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homeostasis/metabolism
growth/size/body
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• decreased weight from early life to adulthood
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skeleton
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• marginally reduced (15%)
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immune system
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• percentage tends to be decreased but is not statistically significant
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7tm2a(EUCOMM)Wtsi mutation
(1 available);
any
Chd7 mutation
(136 available)
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mortality/aging
cardiovascular system
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• about 5% of mutants show a hypoplastic pulmonary trunk at E15.5 and E16.5
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• about 30% of mutants exhibit interrupted aortic arch, type b at E15.5 and E16.5
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• the number of neural crest cells in the proximal outflow tract cushions is reduced at E11.5
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• all mutants exhibit the double outlet right ventricle at E15.5 and E16.5
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• all mutants exhibit a ventricular septal defect at E15.5 and E16.5
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craniofacial
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• E17.5 mutants show a smaller frontal bone
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• E17.5 mutants exhibit a smaller mandible
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• E17.5 mutants exhibit a smaller maxilla
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• 30% of mutants show increased cell death in the pharyngeal arch region
• however, no reduction in cell proliferation is seen in the pharyngeal arch regions at E11.5
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embryo
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• 30% of mutants show increased cell death in the pharyngeal arch region
• however, no reduction in cell proliferation is seen in the pharyngeal arch regions at E11.5
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• marker analysis at E11.5 indicates that differentiation of cranial neural crest cells into smooth muscle cells is reduced
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• cell proliferation in the neural crest cell derivatives, aorta and pulmonary trunk walls, is reduced at E12.5
• 30% of mutants show increased cell death in the pharyngeal arch region
• however, no reduction in cell proliferation is seen in the dorsal neural tube, pharyngeal arch regions and outflow tract cushions at E11.5 and no increase in cell death is seen in the dorsal neural tube and outflow tract cushions at E11.5
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• the number of neural crest cells in the proximal outflow tract cushions is reduced at E11.5 however, no increase in cell death or reduction in cell proliferation is seen in the outflow tract cushions, indicating that cranial neural crest cell migration to outflow tract cushions is reduced
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nervous system
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• marker analysis at E11.5 indicates that differentiation of cranial neural crest cells into smooth muscle cells is reduced
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skeleton
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• E17.5 mutants show a smaller frontal bone
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• E17.5 mutants exhibit a smaller mandible
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• E17.5 mutants exhibit a smaller maxilla
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cellular
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• the number of neural crest cells in the proximal outflow tract cushions is reduced at E11.5 however, no increase in cell death or reduction in cell proliferation is seen in the outflow tract cushions, indicating that cranial neural crest cell migration to outflow tract cushions is reduced
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chd7tm2a(EUCOMM)Wtsi mutation
(1 available);
any
Chd7 mutation
(136 available)
Tg(Tek-cre)1Ywa mutation
(6 available)
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mortality/aging
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• number of live pups recorded at P10 is 5 versus expected 8 (based on Mendelian ratios)
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cardiovascular system
N |
• no embryos exhibit hemorrhaging at E15.5
• no double outlet right ventricle (DORV) or common arterial trunk (CAT) are observed at E15.5, suggesting normal arterial pole septation
• no double inlet left ventricle (DILV) or venous valve defects are observed
• coronary vein development is normal
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• at E15.5, 12.5% of embryos show interrupted aortic arch type B (IAA-B)
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• at E15.5, 37.5% of embryos show myocardial non-compaction
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• at E15.5, 12.5% of embryos show an atrial septal defect (ASD) only
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• at E15.5, 12.5% of embryos exhibit an atrioventricular septal defect (AVSD)
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• at E15.5, 25% of embryos show a ventricular septal defect (VSD) only
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homeostasis/metabolism
muscle
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• at E15.5, 37.5% of embryos show myocardial non-compaction
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mortality/aging
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• only ~75% of embryos survive to E15.5, with no necrotic embryos detected up to E13.5; the number of embryos collected at E18.5 is significantly below the expected Mendelian ratios (2 versus expected 9)
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• no live pups are born or recorded at P10
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cardiovascular system
N |
• at E10.5, all embryos exhibit normal pharyngeal arch artery (PAA) development
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• at E15.5, 21% (3 of 14) of embryos show interrupted aortic arch type B (IAA-B)
• IAA-Bs seen at E15.5 are likely due to a PAA remodeling defect
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• at E15.5, 90% (9 of 10) embryos show absent or poorly formed venous valves
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• at E15.5, coronary veins show either severe truncation of the vessels or ectopic formation of multiple small veins
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• at E15.5, the % of overall thickness of the trabecular layer in the left ventricle is 65% versus 49% in control hearts
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• at E15.5, 80% of embryos show myocardial non-compaction
• however, development of the epicardium appears normal at E13.5
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• at E15.5, the compact myocardial layer of the ventricular wall is thin, esp. in the left ventricle
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• undifferentiated second heart field (SHF) progenitors are normally added to the arterial pole at E11.5, indicating that outflow tract defects are likely due to subsequent differentiation of SHF-derived cells
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• at E13.5, one of 10 embryos shows a common arterial trunk (CAT) where the outflow tract is not fully septated into a separate aorta and pulmonary trunk
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• at E13.5, one of 10 embryos shows an aortopulmonary window above a common set of valves
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• hearts exhibit major septation defects affecting both the arterial and venous poles; great vessel, OFT and septation defects are observed
• at E11.5, the vestibular spine is absent or reduced in size
• at E15.0, cardiac innervation is defective with significantly fewer axonal branch points seen on the dorsal surface of the heart; the % of the dorsal ventricular surface area covered by extending axons is reduced to 27% versus 57% in control hearts
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• at E11.5, the endocardial cushions are abnormally positioned (rotated) within the AV canal
• however, no hypocellular AV cushion defect is noted at t E10.5 or E11.5, indicating that mesenchymal population of the cushions is not affected
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• at E15.5, 60% (6 of 10) of hearts show double outlet arising from the right ventricle (DORV)
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• at E15.5, all (10 of 10) hearts show a common atrioventricular (AV) valve
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• at E15.5, all (10 of 10) hearts show double inlet left ventricle (DILV) including interventricular communication and common atrioventricular (AV) valves
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• at E15.5, all (10 of 10) hearts exhibit an atrioventricular septal defect
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• overall thickness of both the right and left ventricles is significantly reduced
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• at E15.5, 64% of embryos display hemorrhaging
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• ex vivo, only 39% of E13.5 cardiomyocytes respond to electrical pacing with regular Ca2+ transients recorded at the expected 1 s intervals versus 95% of control cells, indicating impaired excitation-contraction coupling
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• at E15.5, over 90% of embryos show severe edema and/or hemorrhaging, indicative of cardiac failure
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homeostasis/metabolism
nervous system
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• at E15.0, cardiac innervation is defective with significantly fewer axonal branch points seen on the dorsal surface of the heart; the % of the dorsal ventricular surface area covered by extending axons is reduced to a 27% versus 57% in control hearts
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muscle
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• at E15.5, the % of overall thickness of the trabecular layer in the left ventricle is 65% versus 49% in control hearts
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• at E15.5, 80% of embryos show myocardial non-compaction
• however, development of the epicardium appears normal at E13.5
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• at E15.5, the compact myocardial layer of the ventricular wall is thin, esp. in the left ventricle
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