Phenotypes Associated with This Genotype

Genotype
MGI:7511685

• Allelic Composition: Chd4^em1Flc/Chd4^em1Flc
• Genetic Background: C57BL/6J-Chd4^em1Flc

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

neonatal lethality, incomplete penetrance ( J:338019 )

• mice die at or shortly after birth, with no mice surviving more than 2 days

postnatal lethality, complete penetrance ( J:338019 )

• mice die at or shortly after birth, with no mice surviving more than 2 days

cardiovascular system

abnormal heart morphology ( J:338019 )

• hearts show immature and poorly aligned mitochondrial cristae

abnormal myocardial fiber morphology ( J:338019 )

• E18.5 heart myofibrils show a severe reduction in myosin filament density and a loss or deformation of Z discs and tropomyosin fails to localize into discrete sarcomeres

abnormal myocardial trabeculae morphology ( J:338019 )

• by E14.5, trabeculae are thicker while the compact layer is thinner and trabeculae fail to fold

• the trabeculae in hearts remain straight and protrude perpendicularly to the compact zones and extend across the lumen compared to wild-type hearts in which trabeculae are folded and oriented parallel to the free wall of the right ventricle

• at E9.5, trabeculae in hearts are longer and protrude into the ventricular cavities and form a ventricular mesh network and by E12.5, hearts show excess trabeculae

• trabecular phenotypes persist at E16.5 and E18.5 but the thickness of the compact zones in the left ventricle are similar to wild-type, indicating a failure to terminate cardiac trabeculation

thin myocardium compact layer ( J:338019 )

• by E12.5, hearts show thinning of the compact layer and the compact layer is thinner at E14.5

• while trabecular phenotypes persist at E16.5 and E18.5, the thickness of the compact zones in the left ventricle are similar to wild-type at these time points

increased cardiac jelly amount ( J:338019 )

• hearts show an increase in Alcian Blue (detects acidic mucopolysaccharides) in the ventricular cardiac jelly at E9.5, E10.5, E12.5, and E13.5 as well as an increase in versican, indicating an accumulation of extracellular matrix

increased fetal cardiomyocyte number ( J:338019 )

• increase in the number of cardiomyocytes in P0 hearts

• however, cardiomyocyte size is not different from controls at P0

abnormal heart ventricle morphology ( J:338019 )

• hearts show severe right ventricular and modest left ventricular noncompaction

thick interventricular septum ( J:338019 )

• increase in the thickness of the ventricular septa

ventricular septal defect ( J:338019 )

• about 20% of hearts show ventricular septal defects

• however, however, no alterations in the development of the aorta and pulmonary artery are seen

thick ventricular wall ( J:338019 )

• increase in the thickness of the ventricular walls

decreased ventricle muscle contractility ( J:338019 )

• left ventricular ejection fraction and left ventricular fractional shortening are reduced

abnormal fetal cardiomyocyte physiology ( J:338019 )

• decrease in cardiomyocytes in the G1 phase and a concomitant increase of cardiomyocytes in the S phase and an increase in G2/M phases

• gene set enrichment analysis shows that cardiomyocytes are in an immature state

increased fetal cardiomyocyte proliferation ( J:338019 )

• cardiomyocytes show an increased and prolonged state of proliferation

abnormal heart echocardiography feature ( J:338019 )

• short-axis M-mode echocardiograms show little ventricular wall movement, severe cardiac contractile dysfunction, reduced left ventricular ejection fraction, left ventricular fractional shortening, right ventricular end-systolic, and diastolic volume at E18.5

decreased heart rate ( J:338019 )

• heart rate is reduced at E18.5

cellular

increased fetal cardiomyocyte proliferation ( J:338019 )

• cardiomyocytes show an increased and prolonged state of proliferation

muscle

abnormal myocardial fiber morphology ( J:338019 )

• E18.5 heart myofibrils show a severe reduction in myosin filament density and a loss or deformation of Z discs and tropomyosin fails to localize into discrete sarcomeres

abnormal myocardial trabeculae morphology ( J:338019 )

• the trabeculae in hearts remain straight and protrude perpendicularly to the compact zones and extend across the lumen compared to wild-type hearts in which trabeculae are folded and oriented parallel to the free wall of the right ventricle

• at E9.5, trabeculae in hearts are longer and protrude into the ventricular cavities and form a ventricular mesh network and by E12.5, hearts show excess trabeculae

• by E14.5, trabeculae are thicker while the compact layer is thinner and trabeculae fail to fold

• trabecular phenotypes persist at E16.5 and E18.5 but the thickness of the compact zones in the left ventricle are similar to wild-type, indicating a failure to terminate cardiac trabeculation

thin myocardium compact layer ( J:338019 )

• by E12.5, hearts show thinning of the compact layer and the compact layer is thinner at E14.5

• while trabecular phenotypes persist at E16.5 and E18.5, the thickness of the compact zones in the left ventricle are similar to wild-type at these time points

decreased ventricle muscle contractility ( J:338019 )

• left ventricular ejection fraction and left ventricular fractional shortening are reduced

increased fetal cardiomyocyte proliferation ( J:338019 )

• cardiomyocytes show an increased and prolonged state of proliferation

abnormal Z line morphology ( J:338019 )

• E18.5 heart myofibrils show a loss or deformation of Z discs

abnormal skeletal muscle fiber morphology ( J:338019 )

• E18.5 hindlimbs have fewer but larger myofibers that are disorganized

increased skeletal muscle fiber size ( J:338019 )

• E18.5 hindlimbs have larger myofibers

decreased skeletal muscle fiber number ( J:338019 )

• E18.5 hindlimbs have fewer myofibers

skeleton

increased width of hypertrophic chondrocyte zone ( J:338019 )

• the distal hypertrophic chondrocyte layer of the tibia is thicker at E18.5

• however, length of the tibial bone is normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
left ventricular noncompaction		DOID:0060480	OMIM:604169	J:338019