Phenotypes Associated with This Genotype

Genotype
MGI:2450526

• Allelic Composition: Tll1^tm1Dgr/Tll1^tm1Dgr
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss

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

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:54910 )

• most homozygous mutant embryos die between E14.5 and E16.5

cardiovascular system

dilated dorsal aorta ( J:54910 )

• at E11.0, mutant dorsal aortae are dilated and filled with blood, consistent with cardiac failure

abnormal descending thoracic aorta morphology ( J:54910 )

• at E13.5, all (16 of 16) homozygotes have a descending aorta that is mispositioned in the center of the embryo, rather than found towards the left of the trachea

abnormal cardinal vein morphology ( J:54910 )

• at E11.0, mutant cardinal veins are dilated and filled with blood, consistent with cardiac failure

abnormal conotruncal ridge morphology ( J:54910 )

• at E13.5, endocardial ridges fail to form properly and fuse, resulting in nonfunctional semilunar valves

failure of atrioventricular cushion closure ( J:54910 )

• at E11.0, the muscular ventricular septum has failed to rise resulting in two un-fused endocardial cushions in the atrio-ventricular canal

double outlet right ventricle ( J:54910 )

• at E13.5, 5 of 16 mutant embryos exhibit a double-outlet right ventricle, where both the normally divided aorta and pulmonary trunk exit the right ventricle

abnormal mitral valve morphology ( J:54910 )

• at E13.5, 8 of 16 homozygotes display a dysplastic mitral valve

double inlet heart left ventricle ( J:54910 )

• at E13.5, 1 of 16 homozygotes display a double-inlet left ventricle, where both atria open into the left ventricle

ostium primum atrial septal defect ( J:54910 )

• at E110.0, all (5 of 5) homozygotes display a large opening between the future left and right atria due to absence of a normal septum primum (the future atrial septum)

abnormal heart position or orientation ( J:54910 )

• at E13.5, all (16 of 16) homozygotes display mispositioning of the entire heart to the left side of the embryo

atrioventricular septal defect ( J:54910 )

• at E13.5, 12 of 16 homozygotes have a balanced atrio-ventricular septal defect with divided orifices, showing aberrant septation of both the ventricles and atria

• at E110.0, all (5 of 5) homozygotes display a large opening between the future left and right atria due to absence of a normal septum primum (the future atrial septum)

ventricular septal defect ( J:54910 )

• at E13.5, all (16 of 16) homozygotes display a large interventricular septal defect beneath the superior bridging leaflet

• however, septation of the common outflow tract into the separate aorta and pulmonary trunk is normal

abnormal semilunar valve morphology ( J:54910 )

• at E13.5, some homozygotes display severely dysplastic semilunar valves where the valvar leaflets are attached to the crest of the ventricular septum and the venous valves are attached to the spina vestibuli

liver hemorrhage ( J:54910 )

• at E13.5, the fetal liver is engorged with blood, consistent with cardiac failure

congestive heart failure ( J:54910 )

• at E13.5, failure to maintain a uni-directional blood flow, combined with a failure to septate the common ventricular chamber results in hemodynamic overload, eventually leading to cardiac failure

homeostasis/metabolism

edema ( J:54910 )

• at E13.5, mutant embryos are severely edematous resulting in damage to the dermis and undelying mesenchyme

integument

pallor ( J:54910 )

• at E13.5, mutant embryos are pale

liver/biliary system

liver hemorrhage ( J:54910 )

• at E13.5, the fetal liver is engorged with blood, consistent with cardiac failure