Phenotypes Associated with This Genotype

Genotype
MGI:2173523

• Allelic Composition: Nodal^tm1Mku/Nodal^tm1.1Mku
• Genetic Background: either: (involves: 129S1/Sv * FVB/N) or (involves: 129S1/Sv * C57BL/6J * FVB/N)

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

mortality/aging

perinatal lethality, complete penetrance ( J:73506 )

• of those alive at E14.5 none survive to birth

embryonic lethality, incomplete penetrance ( J:73506 )

• some die before E14.5

embryo

abnormal developmental patterning ( J:73506 )

abnormal gastrulation ( J:73506 )

• abnormalities in the primitive streak, node, and anterior visceral endoderm suggest that axial rotation is abnormal

• 20% of embryos develop with the anterior region outside the yolk sac (type II) and 29% of embryos develop completely outside the yolk sac (type III), the remainder develop within the yolk sac (type I)

abnormal embryo turning ( J:73506 )

abnormal rostral-caudal axis patterning ( J:73506 )

• expression analysis indicates abnormal cell positions along the anterior posterior axis at E7.5

• defects in axial patterning become more pronounced by E8.5

• severe defects in anterior patterning are seen in all 3 types of embryos

embryonic growth arrest ( J:73506 )

• some embryos arrest prior to gastrulation

abnormal embryonic tissue morphology ( J:73506 )

abnormal lateral plate mesoderm morphology ( J:73506 )

• at E8.5 type III embryos lack any apparent lateral plate mesoderm

• at E8.5 type I embryos lack normal asymmetric gene expression in the left lateral plate mesoderm

abnormal neural fold formation ( J:73506 )

• type I embryos lack the normal ventral midline separation of the neural folds at E8.5

abnormal embryonic neuroepithelium morphology ( J:73506 )

• in type II embryos the head neuroectoderm is disorganized with repeated foldings

absent floor plate ( J:73506 )

• type II embryos lack a distinct floor plate in the trunk region

absent notochord ( J:73506 )

• in some type II embryos

truncated notochord ( J:73506 )

• in some type II embryos the notochord is present in the trunk but ends abruptly at the level of the head

• in type III embryos the notochord end short of the most anterior region

abnormal prechordal plate morphology ( J:73506 )

• type I embryos lack a prechordal plate in the forebrain region at E8.5

absent prechordal plate ( J:73506 )

• in type II and type III embryos

abnormal primitive streak morphology ( J:73506 )

• expression analysis at E7.5 indicates truncation of the primitive streak

abnormal primitive node morphology ( J:73506 )

• at E7.5, the node appears to be more proximal in location compared to controls

• at E8.5 in type II embryos Nodal expressing cells are found across the midline rather than confined to the periphery as in controls

absent primitive node ( J:73506 )

• at E8.5 type III embryos lack a recognizable node

fused somites ( J:73506 )

• all type II embryos show fusion of somites across the midline

• some type III embryos have fused somites

embryonic-extraembryonic boundary constriction ( J:73506 )

• a constriction is present at the boundary

• the lateral edges of the mesodermal wings encroach on the anterior midline at the site where the anterior visceral endoderm normally contacts the underlying anterior embryonic ectoderm

abnormal anterior visceral endoderm morphology ( J:73506 )

• in distal locations cells with cuboidal shapes are present where in controls the cell are squamous in shape

nervous system

abnormal embryonic neuroepithelium morphology ( J:73506 )

• in type II embryos the head neuroectoderm is disorganized with repeated foldings

absent floor plate ( J:73506 )

• type II embryos lack a distinct floor plate in the trunk region

abnormal brain development ( J:73506 )

• type II and type III embryos lack demarcations between fore-, mid- and hindbrain regions

holoprosencephaly ( J:73506 )

• seen in type I embryos at E14.5

digestive/alimentary system

abnormal stomach position or orientation ( J:73506 )

• in a few type I embryos at E14.5 the stomach is located on the right side or shows incomplete rotation

abnormal digestive system development ( J:73506 )

• expression analysis suggests that type III embryos lack gut endoderm and there is no morphologically recognizable gut tube in these embryos

absent foregut ( J:73506 )

• in type II embryos no recognizable foregut pocket is found

truncated foregut ( J:73506 )

• in type I embryos the foregut does not extend as far anteriorly as in controls

abnormal hindgut morphology ( J:73506 )

• abnormally narrow and prematurely closed in type II embryos

cardiovascular system

abnormal direction of heart looping ( J:73506 )

• randomized direction of looping in type I embryos

absent heart tube ( J:73506 )

• type II and type III embryos fail to develop a heart tube

transposition of great arteries ( J:73506 )

• in all type I embryos at E14.5

respiratory system

right pulmonary isomerism ( J:73506 )

• in most type I embryos at E14.5

liver/biliary system

small liver ( J:73506 )

• in some type I embryos at E14.5 the liver is reduced in size and/or pale

pale liver ( J:73506 )

• in some type I embryos at E14.5 the liver is reduced in size and/or pale

growth/size/body

abnormal head development ( J:73506 )

• type II and type III embryos have a ventral orientation of the head

right pulmonary isomerism ( J:73506 )

• in most type I embryos at E14.5