Phenotypes associated with this allele

• Allele Symbol: Nkx2-5^tm1Wehi
• Allele Name: targeted mutation 1, Walter and Eliza Hall Institute of Medical Research
• Allele ID: MGI:1927227
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nkx2-5^tm1Wehi/Nkx2-5^tm1Wehi	involves: 129P2/OlaHsd * C57BL/6J * C57BL/10	MGI:2175149
ht2	Nkx2-5^tm1Wehi/Nkx2-5^+	involves: 129P2/OlaHsd	MGI:5426985
ht3	Nkx2-5^tm1Wehi/Nkx2-5^+	involves: 129P2/OlaHsd * C57BL/6J * C57BL/10J	MGI:3655208
cx4	Hand2^tm1Dsr/Hand2^tm1Dsr Nkx2-5^tm1Wehi/Nkx2-5^tm1Wehi	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:3607709
cx5	Hand2^tm1Dsr/Hand2^+ Nkx2-5^tm1Wehi/Nkx2-5^+	involves: C57BL/6	MGI:3607708

Genotype
MGI:2175149

hm1

• Allelic Composition: Nkx2-5^tm1Wehi/Nkx2-5^tm1Wehi
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * C57BL/10

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:27443 )

• homozygotes die at ~E9.0-E10.0, probably as a result of early hemodynamic insufficiency

cardiovascular system

abnormal myocardium layer morphology ( J:27443 )

• at E9.0-E9.5, mutant hearts lack an association between the endocardium and the myocardial wall

absent trabeculae carneae ( J:27443 )

disorganized myocardium ( J:27443 )

• at E9.0-E9.5, homozygotes show reduced adhesion between myocytes of the inner mural layer of the myocardium

abnormal cardiac outflow tract development ( J:27443 )

• at E8.5, homozygotes display a stepped ventricular-outflow tract junction

abnormal fetal atrioventricular canal morphology ( J:27443 )

• at E8.5, homozygotes exhibit an open atrioventricular (AV) chamber and absence of an AV canal

• at E9-E9.5, some AV demarcation is evident, but the AV canal fails to elongate; the AV chamber becomes distended

absent atrioventricular cushions ( J:27443 )

failure of heart looping ( J:27443 )

• at E8.5, homozygotes fail to initiate looping morphogenesis

abnormal heart tube morphology ( J:27443 )

• at E8.5, homozygotes display an abnormal linear heart tube with a bulbous ventricular chamber

abnormal sinus venosus morphology ( J:27443 )

• after E9.0, homozygotes exhibit distension of the sinus venosus

abnormal heart shape ( J:27443 )

• at >E9.0, mutant hearts exhibit a variably abnormal shape that is often biased towards the left and lacks a dextroloop

abnormal heart ventricle shape ( J:27443 )

• at E8.5, mutant heart tubes remain linear with a bulbous ventricular chamber

pericardial edema ( J:27443 )

• at ~E9.0, homozygotes develop pericardial edema

poor circulation ( J:27443 )

• homozygotes display hemodynamic insufficiency

embryo

embryonic growth retardation ( J:27443 )

• at E8.5 and thereafter, all homozygotes exhibit severe growth retardation

decreased embryo size ( J:27443 )

• at E11, homozygotes exhibit a size comparable to that observed in E8.5-E9.0 wild-type embryos

abnormal somite development ( J:27443 )

• homozygotes deviate from normal development at the 15- to 20-somite stage

incomplete somite formation ( J:27443 )

• homozygotes never develop beyond the 24-somite stage

growth/size/body

embryonic growth retardation ( J:27443 )

• at E8.5 and thereafter, all homozygotes exhibit severe growth retardation

decreased embryo size ( J:27443 )

• at E11, homozygotes exhibit a size comparable to that observed in E8.5-E9.0 wild-type embryos

homeostasis/metabolism

edema ( J:27443 )

• at E9.0, homozygotes begin to develop generalized edema

pericardial edema ( J:27443 )

• at ~E9.0, homozygotes develop pericardial edema

muscle

abnormal myocardium layer morphology ( J:27443 )

• at E9.0-E9.5, mutant hearts lack an association between the endocardium and the myocardial wall

absent trabeculae carneae ( J:27443 )

disorganized myocardium ( J:27443 )

• at E9.0-E9.5, homozygotes show reduced adhesion between myocytes of the inner mural layer of the myocardium

abnormal myogenesis ( J:27443 )

• homozygotes exhibit defective heart myogenesis

Genotype
MGI:5426985

ht2

• Allelic Composition: Nkx2-5^tm1Wehi/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd

hematopoietic system

spleen hypoplasia ( J:184521 )

immune system

spleen hypoplasia ( J:184521 )

Genotype
MGI:3655208

ht3

• Allelic Composition: Nkx2-5^tm1Wehi/Nkx2-5⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * C57BL/10J

cardiovascular system

abnormal interatrial septum morphology ( J:81343 )

• delay or maldevelopment of the septum secundum and an increase in patent foramen ovale and atrial septal aneurysims

atrial septal aneurysm ( J:81343 )

• exhibit a 6-fold increase in atrial septal aneurysims (34.8% vs. 5.9% in wild-type); indicated by a ruffling of the valve over the foramen ovale

atrial septal defect ( J:81343 )

• only rarely exhibit an atrial septal defect

patent cardiac foramen ovale ( J:81343 )

• 3.5-fold increase in patent foramen ovale (66.1% vs. 18.9% of wild-type); indicated by blood passing easily beneath the flap valve

abnormal aortic valve commissure morphology ( J:81343 )

• in some cases, commissural fibrosis

bicuspid aortic valve ( J:81343 )

• exhibit a 7.8-fold increase in frequency of bicuspid aortic valves

thick aortic valve cusps ( J:81343 )

• mild leaflet thickening

aortic valve stenosis ( J:81343 )

• 3 of 35 display a 3-fold increase in blood flow velocity across the aortic valve suggesting aortic stenosis

prolonged PR interval ( J:81343 )

• females show a mild but significant prolongation of the PR interval

Genotype
MGI:3607709

cx4

• Allelic Composition: Hand2^tm1Dsr/Hand2^tm1Dsr; Nkx2-5^tm1Wehi/Nkx2-5^tm1Wehi
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:72600 )

• double homozygotes die between E9.5 and E10.5, i.e. one-half to one day earlier than homozygotes with either single gene disruption

cardiovascular system

abnormal blood vessel morphology ( J:72600 )

• by E9.5, double homozygotes display disruption of the extraembryonic and embryonic vasculature

absent myocardial trabeculae ( J:72600 )

• double homozygotes display no trabeculae and little cardiac jelly in their single dorsal cardiac chamber

abnormal cardiac outflow tract development ( J:72600 )

• double homozygotes exhibit a thin outflow tract

abnormal sinus venosus morphology ( J:72600 )

• in double homozygotes, the posterior part of the single dorsally located cardiac chamber is connected to bilaterally dilated sinus venosae, indicating hemodynamic insufficiency

abnormal heart atrium morphology ( J:72600 )

• at E9.25, double homozygotes display only a single dorsally located cardiac chamber, which is slightly oriented to the left and is molecularly identified as an atrium

• no evidence of a ventral chamber is observed

ventricular hypoplasia ( J:72600 )

• double homozygotes display complete ventricular dysgenesis

• a small pool of cardiomyocytes expressing ventricular-specific markers is observed along the ventral surface of the single atrial chamber, but fails to expand in number and form the ventricular chambers

pericardial effusion ( J:72600 )

• by E9.5, double homozygotes begin to exhibit pericardial effusion, indicating heart failure despite continued rhythmical beating

congestive heart failure ( J:72600 )

muscle

absent myocardial trabeculae ( J:72600 )

• double homozygotes display no trabeculae and little cardiac jelly in their single dorsal cardiac chamber

homeostasis/metabolism

pericardial effusion ( J:72600 )

• by E9.5, double homozygotes begin to exhibit pericardial effusion, indicating heart failure despite continued rhythmical beating

Genotype
MGI:3607708

cx5

• Allelic Composition: Hand2^tm1Dsr/Hand2⁺; Nkx2-5^tm1Wehi/Nkx2-5⁺
• Genetic Background: involves: C57BL/6

mortality/aging

mortality/aging ( J:72600 )

N • double heterozygotes are viable, fertile, and grow normally exhibiting a normal lifespan