Mouse Genome Informatics
hm1
    Nkx2-5tm4Rph/Nkx2-5tm4Rph
either: (involves: 129S1/Sv * 129T2/SvEms) or (involves: 129S1/Sv * C57BL/6J)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• exhibit abnormal heart morphology at E8.5 and E9.5 identical to that of homozygous Nkx2-5tm1Wehi mice


Mouse Genome Informatics
ht2
    Nkx2-5tm4Rph/Nkx2-5+
either: (involves: 129S1/Sv * 129T2/SvEms) or (involves: 129S1/Sv * C57BL/6J)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• Background Sensitivity: septal dysmorphogenesis is most severe on the 129/Sv background, with 17% of hearts showing severe septal malformations bordering on atrial septal defect
• exhibit an increase in the frequency of atrial septal aneurysms, indicated by a ruffling of the valve over the foramen ovale
• Background Sensitivity: 11% of heterozygotes on the mixed 129S1/Sv and C57BL/6J background and 34% on the 129/Sv background exhibit atrial septal aneurysms
• only rarely exhibit an atrial septal defect
• exhibit an increase in the frequency of patent foramen ovale, indicated by blood passing easily beneath the flap valve
• Background Sensitivity: 78% of adults (vs 26% of wild-type) on the mixed 129S1/Sv and C57BL/6J background while 94% of adults (vs. 74% of wild-type) on the 129/Sv background show patent foramen ovale
• all neonates on the C57BL/6J background have a patent foramen ovale and 25% of those have a foramen ovale that is up to 2-fold larger than its maximum size in wild-type
• 2% have bicuspid aortic valves


Mouse Genome Informatics
ht3
    Nkx2-5tm4Rph/Nkx2-5+
either: (involves: 129S1/Sv * C57BL/6 * FVB/N) or (involves: 129S1/Sv * C57BL/6 * Quackenbush Swiss)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• exhibit an increase in patent foramen ovale and atrial septal aneurysms, indicating septum abnormalities
• slight increase in atrial septal aneurysims (3% vs. 0% in wild-type)
• Background Sensitivity: increase in frequency of patent foramen ovale, from 6% to 36% on the mixed C57BL/6 and Swiss background and from 2.65% to 62% on the mixed C57BL/6 and FVB/N background


Mouse Genome Informatics
ht4
    Nkx2-5tm4Rph/Nkx2-5+
involves: 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• left atrial dilation is seen
• left ventricular wall thickness was decreased by 12%
• left ventricular systolic dimension was increased 27% and fractional shortening was decreased by 13%

muscle
• left ventricular systolic dimension was increased 27% and fractional shortening was decreased by 13%


Mouse Genome Informatics
ht5
    Nkx2-5tm2(cre)Rph/Nkx2-5tm4Rph
involves: 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system

immune system


Mouse Genome Informatics
cx6
    Nkx2-5tm4Rph/Nkx2-5tm4Rph
Tbx20tm1.1Rph/Tbx20tm1.1Rph

involves: 129S1/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• double homozygous mice show a combination of the heart abnormalities seen in single homozygotes


Mouse Genome Informatics
cx7
    Nkx2-5tm4Rph/Nkx2-5+
Tbx20tm1.1Rph/Tbx20+

involves: 129S1/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• only 10% of mice at weaning were double heterozygotes suggesting partial embryonic or perinatal lethality

cardiovascular system
• 16% of double heterozygotes had atrial septal defects
• left atrial dilation is seen
• some adult mice with atrial septal defects also display myocyte disarray
• the left ventricle diastolic dimension is mildly but significantly increased
• left ventricular wall thickness was decreased by 40%
• some adult mice with atrial septal defects also display patches of fibrosis in the right ventricular myocardium
• signs of dilated cardiomyopathy are seen but no compensatory myocardial hypertrophy or change in heart weight are detected
• left ventricular systolic dimension was increased 47% and fractional shortening was decreased by 24%

muscle
• signs of dilated cardiomyopathy are seen but no compensatory myocardial hypertrophy or change in heart weight are detected
• left ventricular systolic dimension was increased 47% and fractional shortening was decreased by 24%

homeostasis/metabolism
• some adult mice with atrial septal defects also display patches of fibrosis in the right ventricular myocardium

Mouse Models of Human Disease
OMIM IDRef(s)
Atrial Septal Defect 1; ASD1 108800 J:98489