Phenotypes associated with this allele

• Allele Symbol: Wdfy3^{Tn(pb-Act-RFP)1.1Zhu}
• Allele Name: transposon insertion 1.1, Yuan Zhuang
• Allele ID: MGI:6433103
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Wdfy3^Tn(pb-Act-RFP)1.1Zhu/Wdfy3^Tn(pb-Act-RFP)1.1Zhu	involves: C57BL/6 * FVB/NJ	MGI:6433751

Genotype
MGI:6433751

hm1

• Allelic Composition: Wdfy3^{Tn(pb-Act-RFP)1.1Zhu}/Wdfy3^{Tn(pb-Act-RFP)1.1Zhu}
• Genetic Background: involves: C57BL/6 * FVB/NJ

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

mortality/aging

perinatal lethality, complete penetrance ( J:285853 )

• only 10.8% of homozygous embryos are recovered neonatally but all newborns die within several hours after birth

prenatal lethality, incomplete penetrance ( J:285853 )

• homozygous embryos are present at Mendelian ratios at E10.5 (22.1%); however, the survival rate drops at E12.5 (20% vs expected 25%), E14.5 (14.9%) and E18.5 (14.6%)

homeostasis/metabolism

cyanosis ( J:285853 )

• newborns appear grossly pale or cyanotic

edema ( J:285853 )

• at E14.5, a subset of embryos display peripheral edema

integument

pallor ( J:285853 )

• newborns appear grossly pale or cyanotic

growth/size/body

decreased birth body size ( J:285853 )

• newborns are significantly smaller than wild-type controls

decreased fetal weight ( J:285853 )

• at E18.5, body weight of embryos delivered by Cesarean section is significantly lower than that in wild-type controls

cardiovascular system

abnormal heart morphology ( J:285853 )

• at E14.5, embryos exhibit various congenital heart defects

• transgenic overexpression of a C-terminal fragment of Wdfy3 fails to rescue the cardiac defects

abnormal trabecula carnea morphology ( J:285853 )

• at E14.5, all (17 o 17) embryos exhibit disorganized ventricular trabeculation in both left ventricle (LV) and right ventricle (RV)

• disorganized trabeculation is also observed at E12.5, E13.5 and E15.5

abnormal heart development ( J:285853 )

• at E14.5, mRNA levels of Nkx2-5 (NK2 homeobox 5) and Mef2c (myocyte enhancer factor 2C), two cardiac core transcription factors required for heart formation and development, are significantly decreased in the heart

• at E12.5 and E14.5, cell proliferation is significantly reduced in the myocardium of the LV, RV, and interventricular septum, as determined by the % of BrdU+ cells

• at E14.5, decreased cell proliferation is associated with increased cardiac Cdkn1a (cyclin dependent kinase inhibitor 1A) mRNA and protein levels

• Notch1 signaling is perturbed leading to reduced protein levels of Notch1 intracellular domain (N1ICD) and its downstream targets Hes1 and Hey1, and enhanced full-length (uncleaved) Notch1 protein levels

• no differences in apoptotic cell death are noted in the heart at E12.5 or E14.5

• no change in LC3 II and p62 protein abundance or in ubiquitinated protein levels is noted in the heart at E14.5, indicating normal autophagy

abnormal fetal cardiomyocyte morphology ( J:285853 )

• at E14.5, mRNA levels of two cardiomyocyte specific markers, Myh6 (myosin, heavy polypeptide 6, cardiac muscle, alpha) and Myl2 (myosin, light polypeptide 2, regulatory, cardiac, slow; aka MLC2v), are significantly reduced in the heart, suggesting diminished cardiomyocyte differentiation

double outlet right ventricle ( J:285853 )

• at E14.5, five of 17 (29.4%) embryos display a VSD combined with DORV

overriding aortic valve ( J:285853 )

• at E14.5, six of 17 embryos (35.3%) display a large VSD combined with an overriding aorta

perimembraneous ventricular septal defect ( J:285853 )

• at E14.5, all (17 o 17) embryos exhibit a membranous ventricular septal defect (VSD)

• among these 17 embryos, six (35.3%) show a VSD without an outflow tract (OFT) defect, another six (35.3%) display a large VSD with an overriding aorta, and five (29.4%) display a VSD with double outlet right ventricle (DORV)

• VSD is also observed at E15.5

thin ventricular wall ( J:285853 )

• at E14.5, all (17 o 17) embryos exhibit a thinned ventricular wall

• thinning of the ventricular wall is also observed at E12.5, E13.5 and E15.5

dilated heart ventricle ( J:285853 )

• at E14.5, all (17 o 17) embryos exhibit ventricular dilation

• ventricular dilation is also observed at E12.5, E13.5 and E15.5

muscle

abnormal trabecula carnea morphology ( J:285853 )

• at E14.5, all (17 o 17) embryos exhibit disorganized ventricular trabeculation in both left ventricle (LV) and right ventricle (RV)

• disorganized trabeculation is also observed at E12.5, E13.5 and E15.5

cellular

cellular phenotype ( J:285853 )

N • after vehicle or bafilomycin A1 treatment, primary MEFs isolated from E12.5 embryos show no differences in LC3 II and p62 protein abundance relative to similarly treated wild-type MEFs, indicating a normal autophagic flux

N • no change in general autophagy and selective degradation of protein aggregates is noted in the heart at E14.5