Mouse Genome Informatics
cn1
    Vegfatm2Gne/Vegfatm2Gne
Tg(Tnnt2-cre)5Blh/0

involves: 129/Sv * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• complete lethality is observed after E15.5

growth/size
• at E15.5, mutants are runted

cardiovascular system
• at E12.5, the peritruncal area and ventricular septum lack angiogenic sprouts or coronary plexuses that are observed in controls
• by E14.5, mutants have only a few immature myocardial coronary arteries
• dilated subepicardial veins at E14.5
• at E15.5, mutants have necrotic or ruptured septa
• at E15.5, mutants display cardiac hemorrhages


Mouse Genome Informatics
cn2
    Lims1tm1.1Chen/Lims1tm1.1Chen
Lims2tm1.1Chen/Lims2tm1.1Chen
Tg(Tnnt2-cre)5Blh/0

involves: 129/Sv * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die within 4 weeks
• mice die within 4 weeks

cardiovascular system
• the pectinate muscles in the atrial appendage is abnormal compared to in wild-type mice
• cultured attached cardiomyocytes are smaller than similarly treated wild-type cells
• round P1
• with a bulge at the base of the right ventricle at P20
• the ventricular walls exhibits irregular thickness with a thickened right ventricular free wall and thin left ventricular free wall and septum compared to in wild-type mice
• at P1, myocardium exhibit widened gaps of intercalated disks with disarrayed sarcomeres and distorted Z lines compared to in wild-type mice
• at P10, membranes of the intercalated disk are highly convoluted and gaps are widened unlike in wild-type mice
• the myocardium exhibits disruption of cell-cell adhesion compared to in wild-type mice
• mice exhibit disorganized trabeculae that fail to fuse and incorporate into compact myocardium unlike in wild-type mice
• at P20
• few cardiomyocytes attack to a plate coated in fibronectin, laminin, and collagen compared with wild-type cells
• progressive, resulting in death

homeostasis/metabolism
• at P20
• extensive in the lungs and liver

liver/biliary system

respiratory system

growth/size

muscle
• cultured attached cardiomyocytes are smaller than similarly treated wild-type cells


Mouse Genome Informatics
cn3
    Fgf8tm1.3Mrt/Fgf8tm1.4Mrt
Tg(Tnnt2-cre)5Blh/0

involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
N
• no outflow tract or right ventricle defects are observed at E10.5 and no outflow tract septation defects are seen in term fetuses (J:109474)


Mouse Genome Informatics
cn4
    Bmp4tm1Blh/Bmp4tm3.1Blh
Tg(Tnnt2-cre)5Blh/0

involves: 129S/Sv * Black Swiss * C57BL/6 * DBA/2 * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no neonates are found

cardiovascular system
• at E12.5 about a 20% decrease in proliferation is detected in the atrioventricular cushions but not in other areas of the heart
• present in 80% of embryos at E15.5 - E16.5
• single atrioventricular junction with a common valve

Mouse Models of Human Disease
OMIM IDRef(s)
Atrioventricular Septal Defect; AVSD 606215 J:86001


Mouse Genome Informatics
cn5
    Pdlim5tm1Chen/Pdlim5tm1Chen
Tg(Tnnt2-cre)5Blh/?

involves: 129S1/Sv * 129X1/SvJ * Black Swiss * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• left ventricular chamber size is significantly enlarged
• develop dilated cardiomyopathy starting at 3 months of age
• left ventricular function significantly impaired as measured by fractional shortening

muscle
• develop dilated cardiomyopathy starting at 3 months of age
• left ventricular function significantly impaired as measured by fractional shortening


Mouse Genome Informatics
cn6
    Cxadrtm1Mds/Cxadrtm1.1Mds
Tg(Tnnt2-cre)5Blh/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no live conditional null mice are found at 4 weeks after birth; embryos at E10.5; mice display identical phenotype to Cxadrtm1.1Mds homozygotes

cardiovascular system
• at E10.5, engorgement of the cardinal veins is apparent
• hyperplasia of proximal heart tube is seen at E10.5
• sinuatrial valves located at junction between sinus venosus and atrium in wild-type embryos, are absent


Mouse Genome Informatics
cn7
    Cxadrtm1Mds/Cxadrtm1Mds
Tg(Tnnt2-cre)5Blh/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no live conditional null mice are found at 4 weeks after birth; embryos at E10.5; mice display identical phenotype to Cxadrtm1.1Mds homozygotes

cardiovascular system
• at E10.5, engorgement of the cardinal veins is apparent
• hyperplasia of proximal heart tube is seen at E10.5
• sinuatrial valves located at junction between sinus venosus and atrium in wild-type embryos, are absent


Mouse Genome Informatics
cn8
    Lims1tm1.1Chen/Lims1tm1.1Chen
Tg(Tnnt2-cre)5Blh/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
N
• mice exhibit normal heart morphology and physiology under normal conditions (J:167114)
• following infarct induction
• following infarct induction, mice exhibit reduced fractional shortening and increased infarct size and scar tissue with hemorrhage compared with similarly treated wild-type mice

homeostasis/metabolism
• following infarct induction, mice exhibit reduced fractional shortening and increased infarct size and scar tissue with hemorrhage compared with similarly treated wild-type mice

muscle
• following infarct induction


Mouse Genome Informatics
cn9
    Hand2tm1Cse/Hand2+
Tg(Tnnt2-cre)5Blh/0

involves: 129S1/Sv * C57BL/6J * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• embryos survive at the expected Mendelian ratio until 9.5 dpc, with viablility dropping until 12.5 dpc after which no viable embryos are recovered

cardiovascular system
• at 12.5 dpc, surviving embryos show hypoplastic outflow tract
• at 10.5 dpc severely affected embryos exhibit only a single clearly defined ventricle
• at 12.5 dpc, surviving embryos show hypoplastic right ventricle


Mouse Genome Informatics
cn10
    Bmp4tm3.1Blh/Bmp4tm3.1Blh
Tg(Tnnt2-cre)5Blh/0

involves: 129S6/SvEvTac * C57BL/6 * DBA/2 * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

cardiovascular system
N
• no outflow tract abnormalities are seen (J:86001)
• atrial septal defect similar to that in mice heterozygous for Bmp4tm1Blh and Bmp4tm3.1Blh

Mouse Models of Human Disease
OMIM IDRef(s)
Atrioventricular Septal Defect; AVSD 606215 J:86001


Mouse Genome Informatics
cn11
    Fkbp1atm1.1Shou/Fkbp1atm1Zuk
Tg(Tnnt2-cre)5Blh/0

involves: 129S7/SvEvBrd * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
N
• animals show normal ventricular chamber formation; normal trabeculation and compaction in ventricles are observed (J:195489)


Mouse Genome Informatics
cn12
    Smotm2Amc/Smotm2.1Amc
Tg(Tnnt2-cre)5Blh/0

involves: 129X1/SvJ * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
N
• mice exhibit normal outflow tract development (J:135134)


Mouse Genome Informatics
cn13
    Cenpftm1Dbdr/Cenpftm1Dbdr
Tg(Tnnt2-cre)5Blh/?

involves: C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
N
• development of heart structure is grossly normal (J:185133)
• modest reduction in coronary vasculature
• costamere structure is impaired
• decreased number of myocytes in adults
• intercalated disc number is reduced 3.5 fold in mature ventricles
• trabeculae are thinner and blunted
• smaller ventricles
• weight at 4 days of age is 8.2mg compared to 10.5mg for controls
• internal dimension somewhat increased
• modest reduction in epicardial thickness
• cardiac fibrosis in adults
• decreasing ventricular function with age
• three fold decrease in prenatal myocardiocyte proliferation
• P-P intervals greater than 200 ms
• slowing sinus rhythms
• lower myocyte mitotic rates on days 1-4 after birth

growth/size
• normal to slightly smaller body size

mortality/aging
• 20% mortality in the 12 to 21 month age period

muscle
• costamere structure is impaired
• decreased number of myocytes in adults
• intercalated disc number is reduced 3.5 fold in mature ventricles
• trabeculae are thinner and blunted
• three fold decrease in prenatal myocardiocyte proliferation

cellular
• three fold decrease in prenatal myocardiocyte proliferation