Phenotypes associated with this allele

• Allele Symbol: Nkx2-5^tm3.1Mwc
• Allele Name: targeted mutation 3.1, Mauro W Costa
• Allele ID: MGI:5828836
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nkx2-5^tm3.1Mwc/Nkx2-5^tm3.1Mwc	B6J.Cg-Nkx2-5^tm3.1Mwc/Mwc	MGI:5882086
ht2	Nkx2-5^tm3.1Mwc/Nkx2-5^+	B6J.Cg-Nkx2-5^tm3.1Mwc/Mwc	MGI:5882084

Genotype
MGI:5882086

hm1

• Allelic Composition: Nkx2-5^tm3.1Mwc/Nkx2-5^tm3.1Mwc
• Genetic Background: B6J.Cg-Nkx2-5^tm3.1Mwc/Mwc

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

cardiovascular system

abnormal heart development ( J:239808 )

• this phenotype is more pronounced in this I183P substitution than in I183M substitution mice

abnormal heart looping ( J:239808 )

failure of heart looping ( J:239808 )

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:239808 )

• E9.5 homozygous embryos have dysmorphic hearts arrested at the looping stage, E10.5 homozygous embryos have severe growth retardation and heart abnormalities, including hypoplasia and failed cardiac looping, and no homozygous embryos were found past E11.5

Genotype
MGI:5882084

ht2

• Allelic Composition: Nkx2-5^tm3.1Mwc/Nkx2-5⁺
• Genetic Background: B6J.Cg-Nkx2-5^tm3.1Mwc/Mwc

cardiovascular system

dilated pulmonary artery ( J:239808 )

• E18.5 heart shows increased pulmonary artery diameter, but no abnormality in aortic diameter

abnormal heart morphology ( J:239808 )

• right ventricular dysmorphism with a shift to the base, rounded apex, and misalignment relative to the left ventricle

abnormal atrioventricular node morphology ( J:239808 )

• highly dysmorphic appearance of atrioventricular node region in heterozygotes

abnormal heart apex morphology ( J:239808 )

dilated heart right atrium ( J:239808 )

atrial septal defect ( J:239808 )

• 12% show atrial septal defects, which are not found in control or I183M mutant heterozygotes

patent cardiac foramen ovale ( J:239808 )

• in 88% of heterozgyous adults

abnormal heart right ventricle morphology ( J:239808 )

• at 15 weeks of age the right ventricle displays a shift to the base with a rounded apex relative to controls

dilated heart right ventricle ( J:239808 )

decreased heart right ventricle muscle contractility ( J:239808 )

• significant decrease in right ventricle ejection fraction

abnormal heart electrocardiography waveform feature ( J:239808 )

• under homeostatic nonanesthetized conditions there is increased PQ and QRS and a small tendency for decreased ST intervals, and 3 of 8 heterozygotes showed possible split QRS waves

prolonged PQ interval ( J:239808 )

prolonged QRS complex duration ( J:239808 )

shortened ST segment ( J:239808 )

• small tendency for decreased ST interval

abnormal sinoatrial node conduction ( J:239808 )

sinoatrial block ( J:239808 )

abnormal myocardial fiber physiology ( J:239808 )

• neonatal cardiomyocytes show a decrease in basal and maximal respiration compared with control cardiomyocytes

muscle

abnormal atrioventricular node morphology ( J:239808 )

• highly dysmorphic appearance of atrioventricular node region in heterozygotes

decreased heart right ventricle muscle contractility ( J:239808 )

• significant decrease in right ventricle ejection fraction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
atrial heart septal defect 7		DOID:0110112	OMIM:108900	J:239808
hypoplastic left heart syndrome		DOID:9955	OMIM:241550 OMIM:614435	J:239808
tetralogy of Fallot		DOID:6419	OMIM:187500	J:239808