Phenotypes associated with this allele

• Allele Symbol: Vcl^tm1Eda
• Allele Name: targeted mutation 1, Eileen D Adamson
• Allele ID: MGI:1857730
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Vcl^tm1Eda/Vcl^tm1Eda	involves: 129S1/Sv * 129X1/SvJ * Black Swiss	MGI:2174798
ht2	Vcl^tm1Eda/Vcl^+	involves: 129S1/Sv * 129X1/SvJ * Black Swiss	MGI:3613011

Genotype
MGI:2174798

hm1

• Allelic Composition: Vcl^tm1Eda/Vcl^tm1Eda
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Black Swiss

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:45781 )

• homozygous mutant embryos die between E8.5 and E10.5

• only 16% of mutant embryos survive until E10.5, with fatal degeneration evident at E9.5

nervous system

abnormal embryonic neuroepithelial layer differentiation ( J:45781 )

• by E9.5, the cells of the neuroepithelium are disarrayed and the neuroepithelium layer is distorted, with many cells degenerating

decreased embryonic neuroepithelium thickness ( J:45781 )

• at E8.5, homozygotes display a thinner neuroepithelium layer

abnormal neural tube closure ( J:45781 )

incomplete rostral neuropore closure ( J:45781 )

• at E9.5, mutant cephalic neural folds fail to fuse resulting in an open diocoel; the myelocoel appears small and/or distorted

• by E10.5, all homozygotes show absence of midline fusion of the rostral neural tube, resulting in a cranial bilobular appearance

wavy neural tube ( J:45781 )

decreased brain size ( J:45781 )

• at E9.5, homozygotes exhibit a significantly reduced brain

small brain ventricles ( J:45781 )

• at E9.5, mutant brain ventricles are absent or small

absent brain ventricles ( J:45781 )

• at E9.5, mutant brain ventricles are absent or small

abnormal cranial nerve morphology ( J:45781 )

• at E10.5, homozygotes show paucity of cranial nerve development

small dorsal root ganglion ( J:45781 )

• at E10.5, mutant dorsal root ganglia and nerve tracks appear thin and barely detectable

abnormal spinal nerve morphology ( J:45781 )

• at E10.5, homozygotes show paucity of spinal nerve development

cardiovascular system

decreased myocardial fiber number ( J:45781 )

• at E9.5, homozygotes exhibit a severe reduction in cardiomyocytes

thin myocardium ( J:45781 )

• at E9.5, homozygotes display thin walls with only a few cardiomyocytes present

abnormal heart development ( J:45781 )

• at E9.5, homozygotes display abnormal or significantly delayed cardiac development, resulting in small cardiac structures at E10.5

absent atrioventricular cushions ( J:45781 )

• at E9.5, the endocardium is present but cushions fail to form

delayed heart development ( J:45781 )

• at E9.5

abnormal heart position or orientation ( J:45781 )

• at E9.5, mutant hearts are oriented in a downward slant rather than perpendicular to the spinal cord

small heart ( J:45781 )

• at E9.5, mutant hearts are approximately 50% of wild-type size

absent heart valves ( J:45781 )

• at E9.5, homozygotes show absence of cardiac valve formation

abnormal pericardial cavity morphology ( J:45781 )

• at E10.5, homozygotes display a significantly dilated pericardial cavity

decreased cardiac muscle contractility ( J:45781 )

• at E9.5, mutant hearts fail to contract; however, upon transfer to tissue culture, mutant cardiomyocytes are shown to contract rhythmically

embryo

abnormal ectoderm development ( J:45781 )

• at E9.5, homozygotes show absence of the head ectoderm

abnormal mesoderm development ( J:45781 )

• at E8.5, homozygotes exhibit mesoderm in both embryonic and extraembryonic tissues; however, mutant mesodermal cells are reduced in number and appear more condensed

short rostral-caudal axis ( J:45781 )

• at E8.5, homozygotes display a reduced anterior-posterior axis relative to wild-type embryos

embryonic growth arrest ( J:45781 )

• homozygous mutant embryos fail to develop beyond E10

• at E9.5, mutant embryos are structurally fragile and do not survive fixation and embedding as well as wild-type embryos

embryonic growth retardation ( J:45781 )

• at E8.5, homozygotes show significant developmental retardation relative to wild-type embryos

decreased embryo size ( J:45781 )

• at E9.5-E10, homozygotes are 30%-40% smaller than wild-type embryos

abnormal forelimb bud morphology ( J:45781 )

• at E10.5, homozygotes display asymmetrically positioned forelimb buds

small forelimb buds ( J:45781 )

• at E10.5, homozygotes display small forelimb buds

abnormal neural fold formation ( J:45781 )

• at E8.5, mutant neural folds appear thin and distorted within a malformed neural groove

abnormal embryonic neuroepithelial layer differentiation ( J:45781 )

• by E9.5, the cells of the neuroepithelium are disarrayed and the neuroepithelium layer is distorted, with many cells degenerating

decreased embryonic neuroepithelium thickness ( J:45781 )

• at E8.5, homozygotes display a thinner neuroepithelium layer

abnormal neural tube closure ( J:45781 )

incomplete rostral neuropore closure ( J:45781 )

• at E9.5, mutant cephalic neural folds fail to fuse resulting in an open diocoel; the myelocoel appears small and/or distorted

• by E10.5, all homozygotes show absence of midline fusion of the rostral neural tube, resulting in a cranial bilobular appearance

wavy neural tube ( J:45781 )

decreased somite size ( J:45781 )

• at E9.5, homozygotes display abnormally small somites

failure of somite differentiation ( J:45781 )

• at E9.5, homozygotes display reduced somite density

growth/size/body

abnormal head shape ( J:45781 )

• at E10.5, homozygotes fail to fuse the head structures in the ventral cranial midline and exhibit an abnormal head shape

embryonic growth retardation ( J:45781 )

• at E8.5, homozygotes show significant developmental retardation relative to wild-type embryos

decreased embryo size ( J:45781 )

• at E9.5-E10, homozygotes are 30%-40% smaller than wild-type embryos

craniofacial

abnormal head shape ( J:45781 )

• at E10.5, homozygotes fail to fuse the head structures in the ventral cranial midline and exhibit an abnormal head shape

muscle

decreased myocardial fiber number ( J:45781 )

• at E9.5, homozygotes exhibit a severe reduction in cardiomyocytes

thin myocardium ( J:45781 )

• at E9.5, homozygotes display thin walls with only a few cardiomyocytes present

decreased cardiac muscle contractility ( J:45781 )

• at E9.5, mutant hearts fail to contract; however, upon transfer to tissue culture, mutant cardiomyocytes are shown to contract rhythmically

limbs/digits/tail

abnormal forelimb bud morphology ( J:45781 )

• at E10.5, homozygotes display asymmetrically positioned forelimb buds

small forelimb buds ( J:45781 )

• at E10.5, homozygotes display small forelimb buds

digestive/alimentary system

abnormal foregut morphology ( J:45781 )

• at E8.5, homozygotes exhibit a vestigial foregut

cellular

abnormal cell adhesion ( J:45781 )

• in cultute, MEFs isolated from E10.5 mutant embryos exhibit reduced adhesion to fibronectin, vitronectin, laminin and collagen compared to wild-type MEFs

increased fibroblast proliferation ( J:45781 )

• in cultute, MEFs isolated from E10.5 mutant embryos exhibit a 2-fold increase in the migration rates over fibronectin, vitronectin, laminin and collagen relative to wild-type MEFs

• in addition, the level of focal adhesion kinase (FAK) activity is 3-fold higher relative to the wild-type level

Genotype
MGI:3613011

ht2

• Allelic Composition: Vcl^tm1Eda/Vcl⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Black Swiss

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:92398 )

• heterozygotes display increased mortality following acute hemodynamic stress induced by transverse aortic constriction (TAC), with 33% dying spontaneously during the first 3 to 6 hrs following initial postoperative recovery

• only 30% of heterozygotes survive up to the full 12-week period following TAC versus 100% of wild-type mice

cardiovascular system

abnormal myocardial fiber morphology ( J:92398 )

• heterozygotes exhibit normal costamere distribution but disorganized and widened intercalated disks (ICDs) as well as altered ICD-related protein distribution

• at 4 months, unstressed heterozygotes show misalignment of alpha-actinin containing Z-lines and abnormal myocardial ultrastructure despite preserved cardiac function; myofibrils appear less densely packed and are interrupted occasionally by swollen and disorganized mitochondria

• in heterozygotes, changes in myofibrillar attachment to Z-lines and ICDs become even more pronounced after TAC-induced stress, whereas no alterations occur in stressed wild-type mice

abnormal intercalated disk morphology ( J:92398 )

decreased ventricle muscle contractility ( J:92398 )

• heterozygotes show no significant changes in baseline ventricular function as determined by invasive catheterization or echocardiography up to 18 months of age

• however, beginning at 6 weeks post-TAC, heterozygotes exhibit decreased left ventricular function associated with an increased end-systolic dimension

abnormal heart electrocardiography waveform feature ( J:92398 )

• heterozygotes develop normally and display normal basal cardiac function and histology but show abnormal baseline electrocardiograms relative to wild-type mice

prolonged QRS complex duration ( J:92398 )

• electrocardiograms indicate normal PR duration but significantly prolonged QRS complexes in heterozygotes relative to wild-type mice

• no significant differences are detected in heart rate, pressure, or hemodynamic responses at baseline or after adrenergic stimulation

muscle

abnormal myocardial fiber morphology ( J:92398 )

• heterozygotes exhibit normal costamere distribution but disorganized and widened intercalated disks (ICDs) as well as altered ICD-related protein distribution

• at 4 months, unstressed heterozygotes show misalignment of alpha-actinin containing Z-lines and abnormal myocardial ultrastructure despite preserved cardiac function; myofibrils appear less densely packed and are interrupted occasionally by swollen and disorganized mitochondria

• in heterozygotes, changes in myofibrillar attachment to Z-lines and ICDs become even more pronounced after TAC-induced stress, whereas no alterations occur in stressed wild-type mice

abnormal intercalated disk morphology ( J:92398 )

decreased ventricle muscle contractility ( J:92398 )

• heterozygotes show no significant changes in baseline ventricular function as determined by invasive catheterization or echocardiography up to 18 months of age

• however, beginning at 6 weeks post-TAC, heterozygotes exhibit decreased left ventricular function associated with an increased end-systolic dimension