Phenotypes Associated with This Genotype

Genotype
MGI:7545224

• Allelic Composition: Rac1^tm1Djk/Rac1^tm1Djk; Tg(Nkx2-5-cre)9Eno/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6

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

mortality/aging

perinatal lethality, complete penetrance ( J:321017 )

• although mice are alive from E11.5 to E18.5, all neonates are found dead at P0

cardiovascular system

abnormal cardiac outflow tract development ( J:321017 )

• at E14.5-P0, hearts exhibit impaired alignment of the outflow tract (OFT) to the ventricles

abnormal heart morphology ( J:321017 )

• at E14.5-P0, all (17 of 17) hearts display more than one type of congenital heart defect (CHD), not observed in control hearts

abnormal myocardium compact layer morphology ( J:321017 )

• at E15.5, the compact myocardium of both ventricles is poorly formed

thin myocardium compact layer ( J:321017 )

• at E14.5-P0, all hearts (17 of 17) exhibit a thin compact myocardium

thin ventricle myocardium compact layer ( J:321017 )

• at E15.5, both the left ventricle (LV) and right ventricle (RV) show a significant decrease in compact myocardium thickness relative to controls

abnormal ventricle myocardium morphology ( J:321017 )

• at E18.5, the ventricular myocardium shows severe disruption of F-actin filament organization

• at E9.5, the cell proliferation rate in the ventricular myocardium is significantly lower than in control hearts, as assessed by the percentage of pHH3+ and cyclin D1+ cardiomyocytes

• however, no aberrant apoptosis is detected in the ventricular myocardium at E9.5

abnormal trabecula carnea morphology ( J:321017 )

• at E15.5, both the left ventricle (LV) and right ventricle (RV) show hypertrabeculation; the trabecular to compact myocardium ratio is increased by >2.5-fold relative to controls

abnormal heart development ( J:321017 )

• at E12.5, mRNA expression of Scrib and other cardiac transcription and growth factors (Nkx2.5, Gata4, Tbx5, Tbx20, Hand1, Hand2 and Bmp10) is significantly decreased relative to control hearts

abnormal fetal cardiomyocyte morphology ( J:321017 )

• at E18.5, cardiomyocytes in the ventricular myocardium exhibit a rounded morphology and appear highly disorganized in both the RV and LV while the short axis of cardiomyocyte diameter is significantly larger than in controls, indicating impaired cardiomyocyte polarization and elongation

• at E15.5, overall expression of SCRIB (scribble planar cell polarity protein) is significantly reduced in the myocardium surrounding the aorta (OFT), RV and LV, supporting a failure of cardiomyocytes to undergo polarization

double outlet right ventricle ( J:321017 )

• at E14.5-P0, 64.7% (11 of 17) hearts exhibit DORV: both pulmonary artery and aorta are connected to the right ventricle

overriding aortic valve ( J:321017 )

• at E14.5-P0, 35.3% (6 of 17) hearts exhibit and overriding aorta

abnormal heart apex morphology ( J:321017 )

• at E14.5-P0, all (17 of 17) hearts show a bifid cardiac apex (a bifurcation between the right and the left ventricle)

ventricular septal defect ( J:321017 )

• at E14.5-P0, all hearts (17 of 17) show ventricular septal defects

decreased fetal cardiomyocyte proliferation ( J:321017 )

• at E9.5, the cell proliferation rate in the ventricular myocardium is significantly lower than in control hearts, as assessed by the percentage of pHH3+ and cyclin D1+ cardiomyocytes

cellular

decreased fetal cardiomyocyte proliferation ( J:321017 )

• at E9.5, the cell proliferation rate in the ventricular myocardium is significantly lower than in control hearts, as assessed by the percentage of pHH3+ and cyclin D1+ cardiomyocytes

muscle

abnormal myocardium compact layer morphology ( J:321017 )

• at E15.5, the compact myocardium of both ventricles is poorly formed

thin myocardium compact layer ( J:321017 )

• at E14.5-P0, all hearts (17 of 17) exhibit a thin compact myocardium

thin ventricle myocardium compact layer ( J:321017 )

• at E15.5, both the left ventricle (LV) and right ventricle (RV) show a significant decrease in compact myocardium thickness relative to controls

abnormal ventricle myocardium morphology ( J:321017 )

• at E18.5, the ventricular myocardium shows severe disruption of F-actin filament organization

• at E9.5, the cell proliferation rate in the ventricular myocardium is significantly lower than in control hearts, as assessed by the percentage of pHH3+ and cyclin D1+ cardiomyocytes

• however, no aberrant apoptosis is detected in the ventricular myocardium at E9.5

abnormal trabecula carnea morphology ( J:321017 )

• at E15.5, both the left ventricle (LV) and right ventricle (RV) show hypertrabeculation; the trabecular to compact myocardium ratio is increased by >2.5-fold relative to controls

decreased fetal cardiomyocyte proliferation ( J:321017 )

• at E9.5, the cell proliferation rate in the ventricular myocardium is significantly lower than in control hearts, as assessed by the percentage of pHH3+ and cyclin D1+ cardiomyocytes