Phenotypes associated with this allele

• Allele Symbol: Daam1^tm1.1Tpy
• Allele Name: targeted mutation 1.1, Terry Yamaguchi
• Allele ID: MGI:6149780
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Daam1^tm1.1Tpy/Daam1^tm1.1Tpy Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor^+ Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S4/SvJaeSor * 129S7/SvEvBrd	MGI:6150944
cn2	Daam1^tm1.1Tpy/Daam1^tm1.1Tpy Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:6150918
cn3	Daam1^tm1.1Tpy/Daam1^tm1.1Tpy Daam2^tm1Tpy/Daam2^tm1Tpy Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:6150919
cn4	Daam1^tm1.1Tpy/Daam1^tm1.1Tpy Nkx2-5^tm1(cre)Rjs/Nkx2-5^+ Wnt5a^tm1Amc/Wnt5a^tm1Amc	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:6150926
cn5	Daam1^tm1.1Tpy/Daam1^tm1.1Tpy Nkx2-5^tm1(cre)Rjs/Nkx2-5^+ Wnt5a^tm1Amc/Wnt5a^+	involves: 129S1/Sv * 129S7/SvEvBrd	MGI:6151066

Genotype
MGI:6150944

cn1

• Allelic Composition: Daam1^tm1.1Tpy/Daam1^tm1.1Tpy; Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor⁺; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * 129S7/SvEvBrd

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

muscle

abnormal cardiac muscle tissue morphology ( J:228507 )

• in E13.5 embryos

• cardiomyocytes smaller, rounded and loosely attached to each other with thin cellular projections in conotruncal regions

• absent thick protrusions from leading edges of cardiomyocytes invading non-myocardial tissue

• cardiomyocytes randomly distributed and mixed with endocardial cells at bases of blood vessels

cardiovascular system

abnormal cardiac muscle tissue morphology ( J:228507 )

• in E13.5 embryos

• cardiomyocytes smaller, rounded and loosely attached to each other with thin cellular projections in conotruncal regions

• absent thick protrusions from leading edges of cardiomyocytes invading non-myocardial tissue

• cardiomyocytes randomly distributed and mixed with endocardial cells at bases of blood vessels

Genotype
MGI:6150918

cn2

• Allelic Composition: Daam1^tm1.1Tpy/Daam1^tm1.1Tpy; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd

cardiovascular system

cardiovascular system phenotype ( J:228507 )

N • pulmonary artery and aorta in E16.5 embryos

abnormal myocardial trabeculae morphology ( J:228507 )

• in E16.5 embryos

• thicker ventricular trabecular zones, extending into lumen

• inconsistent size of right ventricular trabeculae

• irregular spacing of right ventricular trabeculae

• disorganized left ventricular trabeculae

• left ventricular trabeculae occupy much of ventricular lumen

thin ventricle myocardium compact layer ( J:228507 )

• in E16.5 embryos

abnormal heart left ventricle morphology ( J:228507 )

• in E16.5 embryos

• disorganized

• occupy much of lumen

• thicker trabecular zones

• thinner compact zones

abnormal heart right ventricle morphology ( J:228507 )

• in E16.5 embryos

• free wall does not extend as close to heart apex of 8-months old mice as in control mice

• base closer to tricuspid valve than in controls

• base not aligned with base of left ventricle

• thicker trabecular zones

• thinner compact zones

• inconsistent size of trabeculae

• irregular spacing of trabeculae

abnormal diastolic filling velocity ( J:228507 )

• mean E/A ratio (flow velocity across mitral valve early in diastole divided by that late in diastole) in left ventricle of 2-months old mice is less than 1 in 8-months old mice, compared to greater than 1 in control mice

decreased right ventricle systolic pressure ( J:228507 )

• in 8-months old mice

• lower acceleration of pulmonary artery (PA) flow, indicating reduced RV contraction force

• reduced fractional shortening

abnormal pulmonary pressure ( J:228507 )

• lower acceleration of pulmonary artery (PA) flow in 8-months old mice

muscle

abnormal myocardial trabeculae morphology ( J:228507 )

• in E16.5 embryos

• thicker ventricular trabecular zones, extending into lumen

• inconsistent size of right ventricular trabeculae

• irregular spacing of right ventricular trabeculae

• disorganized left ventricular trabeculae

• left ventricular trabeculae occupy much of ventricular lumen

thin ventricle myocardium compact layer ( J:228507 )

• in E16.5 embryos

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
intrinsic cardiomyopathy		DOID:0060036		J:228507

Genotype
MGI:6150919

cn3

• Allelic Composition: Daam1^tm1.1Tpy/Daam1^tm1.1Tpy; Daam2^tm1Tpy/Daam2^tm1Tpy; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd

cardiovascular system

cardiovascular system phenotype ( J:228507 )

N • compact layer width in E17.5 embryos

abnormal myocardial fiber morphology ( J:228507 )

• in 2-months old mice

• disturbed A-band marker Actc1 striation pattern

• nearly absent intermediate filament Desmin striation

• shorter A-bands

• Z-bands faint or absent

• no apparent I-bands, H-bands or M-lines

• intersecting and disorganized thick fibers in severely affected areas

abnormal intercalated disk morphology ( J:228507 )

• lower-density material frequently observed between membranes of adjacent cardiomyocytes in 2-months old mice through electron microscopy

abnormal myocardial trabeculae morphology ( J:228507 )

• in E17.5 embryos

• failure of trabeculae to assimilate into compact zone, resulting in occluded ventricular lumens

• wider trabecular layers

• thicker individual trabeculae

• inter-trabecular spaces filled with detached endothelial cells

heart hypoplasia ( J:228507 )

• in 2-months old mice

abnormal heart left ventricle morphology ( J:228507 )

• in 2-months old mice

• thicker walls and septa

• smaller lumen

abnormal heart right ventricle morphology ( J:228507 )

• in 2-months old mice

• thicker walls and septa

• smaller lumen

decreased left ventricle systolic pressure ( J:228507 )

• in 2-months old mice

• lower ejection fraction

• reduced fractional shortening

decreased right ventricle systolic pressure ( J:228507 )

• in 2-months old mice

• acceleration of pulmonary artery (PA) flow

• reduced fractional shortening

abnormal myocardial fiber physiology ( J:228507 )

• increased cardiomyocyte proliferation

muscle

abnormal myocardial fiber morphology ( J:228507 )

• in 2-months old mice

• disturbed A-band marker Actc1 striation pattern

• nearly absent intermediate filament Desmin striation

• shorter A-bands

• Z-bands faint or absent

• no apparent I-bands, H-bands or M-lines

• intersecting and disorganized thick fibers in severely affected areas

abnormal intercalated disk morphology ( J:228507 )

• lower-density material frequently observed between membranes of adjacent cardiomyocytes in 2-months old mice through electron microscopy

abnormal myocardial trabeculae morphology ( J:228507 )

• in E17.5 embryos

• failure of trabeculae to assimilate into compact zone, resulting in occluded ventricular lumens

• wider trabecular layers

• thicker individual trabeculae

• inter-trabecular spaces filled with detached endothelial cells

abnormal A band morphology ( J:228507 )

• disturbed A-band marker Actc1 striation pattern and shorter A-bands in cardiomyocytes of 2-months old mice

abnormal H zone morphology ( J:228507 )

• no apparent H-bands in cardiomyocytes of 2-months old mice

absent M line ( J:228507 )

• no apparent M lines in cardiomyocytes of 2-months old mice

abnormal I band morphology ( J:228507 )

• no apparent I-bands in cardiomyocytes of 2-months old mice

absent Z line ( J:228507 )

• in cardiomyocytes of some 2-months old mice

diffuse Z line ( J:228507 )

• in cardiomyocytes of some 2-months old mice

Genotype
MGI:6150926

cn4

• Allelic Composition: Daam1^tm1.1Tpy/Daam1^tm1.1Tpy; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺; Wnt5a^tm1Amc/Wnt5a^tm1Amc
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd

cardiovascular system

abnormal heart morphology ( J:228507 )

• right ventricle shifted anterior to left ventricle in E12.5 embryos

• AV cushion atop single ventricle connected to both atria in some embryos in E12.5 embryos

abnormal myocardial trabeculae morphology ( J:228507 )

• rudimentary in left ventricle of E16.5 embryos

abnormal myocardium compact layer morphology ( J:228507 )

• rudimentary in left ventricle of E16.5 embryos

abnormal interventricular septum morphology ( J:228507 )

• shorter than controls, not extended to the endocardial cushion in the atrioventricular canal in E12.5 embryos

abnormal heart right ventricle morphology ( J:228507 )

• mesenchyme-like organization of cardiomyocytes at ventricle base in E12.5 embryos

• right ventricle shifted anterior to left ventricle in E12.5 embryos

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:228507 )

• very few embryos seen at E16.5 and those that are, are mostly necrotic

muscle

abnormal myocardial trabeculae morphology ( J:228507 )

• rudimentary in left ventricle of E16.5 embryos

abnormal myocardium compact layer morphology ( J:228507 )

• rudimentary in left ventricle of E16.5 embryos

Genotype
MGI:6151066

cn5

• Allelic Composition: Daam1^tm1.1Tpy/Daam1^tm1.1Tpy; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺; Wnt5a^tm1Amc/Wnt5a⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd

cardiovascular system

abnormal myocardial trabeculae morphology ( J:228507 )

• thicker right ventricular trabecular zones, extending into lumen in E16.5 embryos

thick myocardium compact layer ( J:228507 )

• in right ventricle of E16.5 embryos

muscle

abnormal myocardial trabeculae morphology ( J:228507 )

• thicker right ventricular trabecular zones, extending into lumen in E16.5 embryos

thick myocardium compact layer ( J:228507 )

• in right ventricle of E16.5 embryos