Analysis Tools
reproductive system
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• imperforated vagina in some mice
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Allele Symbol Allele Name Allele ID |
Vangl2Lp loop tail MGI:1857642 |
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| Summary |
68 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• imperforated vagina in some mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• failure of neural tube closure 1 between the 5- and 8-somite stages
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• failure of neural tube closure 1 between the 5- and 8-somite stages
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• fully penetrant
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• fully penetrant
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• while alive in the last few days of gestation, homozygotes do not survive birth
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• at E15 all elements are present but appear somewhat flattened
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• at E8.5 the otic pit is ill-defined and somewhat misshapen
• at E9.0 the otic pit is poorly defined, tends to have a deeper slit-like portion, and the cell are flattened, less densely arranged and have microvilli that are disorganized and distorted
• at E9.5 the otic pit lacks the oval shape seen in control littermates, ventrally the border tends to be flattened and less defined, and the epidermal cells tend to be more irregular in shape with flattened surfaces
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• abnormalities are similar to those in Pax3Sp homozygotes but with increased severity
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• inner hair cells are misoriented compared to in wild-type mice
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• outer hair cells are misoriented compared to in wild-type mice
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• formation is partially or completely suppressed
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• grossly enlarged
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• at E12.5 a hemorrhagic area is present in the flap of metencephalon
(J:12992)
• hemorrhage in the flap of metencephalon is also seen in some (3 of 12) embryos at E10.5 - E11.5
(J:12992)
• in the last few days before birth the neural tracts are generally fractured across the lumbar region with considerable hemorrhage
(J:13059)
• into the amniotic cavity in some embryos
(J:133114)
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• abnormal concave flexure of the back suggests that embryos do not complete rotation at E14.5 - E19.5
• Background Sensitivity: in a study looking at 6 inbred lines, impairment of rotation appears to be more severe in one line (8) than in other lines (16, 44, 55,66, 71)
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• markedly smaller at E14.5 - E19.5
(J:12992)
• reduction in size is not proportional in all parts of the body with the trunk seeming relatively short and the nervous system relatively large for the body
(J:12992)
• slightly smaller than wild-type or heterozygous littermates
(J:13059)
• in later stages
(J:133114)
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• crooks in the back are frequently seen in embryos at E14.5 - E19.5
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• at E10.5 - E12.5, cell density in portions of the mantle layer of the hindbrain and cord appears to be reduced
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• extends from the midbrain to varying levels of the tail
(J:5550)
• at E14.5 - E19.5, neural tissue from the posterior border of the metencephalon back is a flat plate with a deep median groove
(J:12992)
• in some embryos flaps of more posterior tissue overlie the diencephalon and sometimes the cerebral hemispheres
(J:12992)
• at E10 the neural tissue fails to form a tube and is instead a herniated cranial mass with two broad tracts separated by a narrow groove down the back
(J:13059)
• in the last few days before birth the neural tracts are generally fractured across the lumbar region
(J:13059)
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• at E9.5 the notochord is shorter with an increase in the diameter and extent of the posterior thickened portion compared to control littermates
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• at E9 - E9.5, the primitive streak is thicker and longer compared to age-matched control littermates
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• at E9.5 posterior somites are often very small and/or irregular in shape
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• at E9.5 posterior somites are often very small and/or irregular in shape
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• at E10 - 11, apparent fusion of some somites is seen associated with torsion of the body
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• at E19 - E20, average cord length is decreased compared to wild-type and heterozygous littermates
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• at E13 - 14, the separation between the right and left sternal rudiements is increased and the rudiments are less dense compared to control littermates
• at E16 the omosterna is less well developed
• in newborns the sternum is a single solid asymmetrical bone with variable numbers of lateral extensions and without normal segmentation
• lateral extensions are usually tipped with cartilage and extend towards the tips of the ribs
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• absence of sternebra formation at E16
• at E17 only rarely is any separation into sternebrae detected
• in some newborns cases partial segmentation of the sternum is seen but the sternebrae are abnormal in size, shape and number
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• at E13 - 14, ribs fail to contact or just barely contact the mesenchymal sternal bands compared to controls where the ribs appear to be embedded in the sternal bands
• at E16 connection between the ribs and sternal cartilages is absent instead distorted sternal rudiments extend towards the ribs
• at E17 the rib tips are more widely separated from the sternum than in control littermates
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• the number and size of ossification centers at E17 is normal but the centers are usually asymmetrical and irregular in shape and sometimes fused
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• at E16 the xiphoid process appears as a mesenchymal condensation and is not chondrified
• the cartilaginous bifurcated section is larger than in newborn wild-type littermates
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• vertebral parapophyses fail to form and no good articulation between veterbrae and ribs develops
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• at E17 ribs are irregular in shape, asymmetrical and frequently bifurcated
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• ossification is somewhat delayed in some embryos and development in all embryos is irregular
• ribs are less likely to show the normal size taper pattern
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• otal number of ribs on either side tends to be decreased with the number of ribs per side frequently different and correlated to the direction of torsion of the body (i.e. animals with a right twist have fewer right ribs)
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• bifurcation of about 1/3 of the length of the rib is frequently detected at E17
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• detectable from the earliest appearance of the ribs (around E12) and correlated with bending or torsion of the body
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• extremely misshapen
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• ossification centers are usually later to appear and more irregular in size and shape
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• do not form normally
• parapophyses fail to form
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• neural arches fail to form normally around the open, flat neural tube and are seen to puncture the flattened neural folds
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• centra are abnormal in size, shape and position and frequently fused
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• centra are frequently fused
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• frequently fuse to form longitudinal bars of variable length and shape
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• at E10.5 - E12.5, cell density in portions of the mantle layer of the hindbrain and cord appears to be reduced
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• extends from the midbrain to varying levels of the tail
(J:5550)
• at E14.5 - E19.5, neural tissue from the posterior border of the metencephalon back is a flat plate with a deep median groove
(J:12992)
• in some embryos flaps of more posterior tissue overlie the diencephalon and sometimes the cerebral hemispheres
(J:12992)
• at E10 the neural tissue fails to form a tube and is instead a herniated cranial mass with two broad tracts separated by a narrow groove down the back
(J:13059)
• in the last few days before birth the neural tracts are generally fractured across the lumbar region
(J:13059)
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• inner hair cells are misoriented compared to in wild-type mice
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• outer hair cells are misoriented compared to in wild-type mice
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• in some embryos a large flap-like extension of neural tissue overhangs the face
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• at E9.5 the neural anlage in the region of the floor is shorter compared to control littermates
(J:12992)
• the number of mitotic figures is increased in the brain but not in the spinal cord
(J:133114)
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• at E10 and E11 in ventricular cells of the tectum, the mitotic index is increased, generation time is increased, and M, G1 and S (on E11 only) phases of the cell cycle are prolonged
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• at E10 mesencephalon cells lack microvilli but retain a fairly normal cilium
(J:5544)
• at E12 - E14, flattened cells with apparently everted edges and deep depressions spanning multiple cells are present in lateral regions
(J:5544)
• at E10, mesencephalic tissue protrudes creating a median dorsal extension
(J:133114)
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• at E10 the lumen is collapsed
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• in some cases the cerebral hemispheres are collapsed at E14.5 - E19.5
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• at E10, the ventral midline groove is shallower and cells of the groove are less densely covered with microvilli and bulbous processes
• at E11 the cells are flattened, lack microvilli and have less prominent bulbous processes
• at E12 - E14, flattened cells with apparently everted edges and deep depressions spanning multiple cells are present in lateral regions
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• at E10.5, the roof of the metencephalon appears stretched and some cells have pulled apart
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• at E9.5 the gut is shorter compared to control littermates
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• markedly smaller at E14.5 - E19.5
(J:12992)
• reduction in size is not proportional in all parts of the body with the trunk seeming relatively short and the nervous system relatively large for the body
(J:12992)
• slightly smaller than wild-type or heterozygous littermates
(J:13059)
• in later stages
(J:133114)
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• Background Sensitivity: at E14.5 - E19.5, hernias in which the liver and intestines are found outside the body wall are seen in one line (8) while 5 other inbred lines of this allele lack hernias (16, 44, 55,66, 71)
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• in a fair number of embryos small hernias are detected
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• in 2 embryos complete failure of ventral closure is seen with the heart, lungs, liver, and intestines exposed
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• at E8.5 the otic pit is ill-defined and somewhat misshapen
• at E9.0 the otic pit is poorly defined, tends to have a deeper slit-like portion, and the cell are flattened, less densely arranged and have microvilli that are disorganized and distorted
• at E9.5 the otic pit lacks the oval shape seen in control littermates, ventrally the border tends to be flattened and less defined, and the epidermal cells tend to be more irregular in shape with flattened surfaces
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E14.5 and E18.5, mutant lungs show cytokeletal defects and disordered epithelial airways with no apparent disruption of adherens junctions
• however, apical-basal polarity remains intact
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• at E14.5, a significant reduction in the number of epithelial branches is observed
• in explant cultures, mutant E11.5 lung endoderm denuded of mesenchyme responds to a chemoattractant FGF10 stimulus in terms of growth but is unable to undergo branching
• however, no significant changes in epithelial cell differentiation are observed in vivo at E18.5
• also, no significant changes in proliferation or apoptosis are noted at E11.5 or E14.5
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• at E18.5, mutant lungs show atypical saccular structure with no evidence of septation
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• at E18.5, mutant lungs display a thickened interstitial mesenchyme
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• at E14.5, the mutant lung epithelium is improperly aligned and shows a multilayered and/or disorganized morphology, unlike the single layer of uniformly aligned columnar epithelium seen in wild-type lungs
• at E14.5, mutant lung epithelial cells are highly disorganized and randomly orientated with either small or no lumina, and not readily distinguishable from surrounding mesenchyme by DAPI labeling
• Vangl2Lp airways appear less severely affected than Celsr1Crsh airways
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• at E18.5, mutant lung lobes are visibly misshapen
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• at E18.5, mutant lung lobes are smaller than wild-type lobes
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• at E18.5, mutant lungs are smaller than wild-type, likely due to the reduced width and number of airway lumina and increased compaction of the lung tissue
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• at E18.5, mutant lungs are hypoplastic
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• at E14.5, most airway lumina are narrow or absent
• at E18.5, the number and width of mutant airways is severely reduced while the luminal space often contains cells
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• after 48 hrs in ex vivo culture, mutant E11.5 lungs are smaller with significantly fewer and larger terminal buds than wild-type lungs
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• after 48 hrs in ex vivo culture, mutant E11.5 lungs display significantly enlarged terminal buds relative to wild-type lungs
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E9.5 - E10.5, neural tube is open from the hindbrain to the caudal extremity
• however, initiation of closure of the cranial neural tube at the midbrain/forebrain boundary is similar to wild-type
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• at E9.5 - E10.5, neural tube is open from the hindbrain to the caudal extremity
• however, initiation of closure of the cranial neural tube at the midbrain/forebrain boundary is similar to wild-type
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• marked broadening and flattening of the neural plate ventral midline at E8.5
• fail to develop a sharp midline bending at E8.5
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• failure to initiate neural tube closure at the cervical/hindbrain boundry
• neural tube is open throughout the hindbrain and spinal region
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| N |
• more anterior neural fold development is more like controls
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• marked broadening and flattening of the neural plate ventral midline at E8.5
• fail to develop a sharp midline bending at E8.5
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• failure to initiate neural tube closure at the cervical/hindbrain boundry
• neural tube is open throughout the hindbrain and spinal region
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• enlarged
• loosely organized
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• poorly condensed
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• irregularly shaped
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• sternal defects
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• multiple rib fusions
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• neural arches are unfused dorsally
• unfused arches are splayed apart
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| neural tube defect | DOID:0080074 |
OMIM:301410 OMIM:601634 |
J:47700 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E9.5
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• at E9.5
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• midline is shorter and wider at the 1 to 4 somite stage
• change in size is not due to changes in cell shape
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• significantly shorter and wider
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• at E9.5
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• at E9.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Vangl1Gt(XL802)Byg/Vangl1+ Vangl2Lp/Vangl2+ and Vangl2Lp/Vangl2Lp embryos exhibit aberrant right subclavian artery
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• reduced in size at E18.5
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• shorter, wider cochlear ducts
• inner ears from E15.5 cultured for 6 days fail to grow in length, have misoriented stereocilia, and widened apex
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• increased rows of hair cells within the third of the cochlea nearest the apex
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• 70% of inner hair cell bundles are misoriented
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• misorientation of stereociliary bundles at E18.5, more severe in the medial region than the base with approximately 95% misoriented in the two outer rows of outer hair cells
(J:100861)
• a significant proportion of bundles in all 3 layers are misoriented
(J:132697)
• vertices are randomly oriented with rotation angles of 40 - 180 degrees
(J:132697)
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• narrowing or interruption of the left aortic arch in about 40% of mice
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• at E14.5, the right subclavian artery is positioned dorsal to the esophagus
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• in 2 of 6 at E13.5 with retroesophageal left subclavian artery
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• in 4 of 6 mice at E13.5 and in 3 of 3 at E18.5
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• at E13.5 2 of 6 show right aortic-sided arch with retroesophageal left subclavian artery
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• in some cases (3 of 18) the aortic and pulmonary valves appear as a common valve
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• at E12.5, myocardial cells do not appear to extend as far into the septum as in control littermates and myocardial cells fail to extend lamellipodia or filopodia into the endocardial cushion tissue
• at E13.5, fewer cardiomyocytes extend into the septum, the boundary of the myocardial wall and mesenchymal septum does not follow a smooth curve, and the non-muscularized region of the proximal outlet septum appears larger
• at E15.5, the outlet septum is malpositioned and not muscularized and the aorta maintains contact with the right ventricle
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• at E8.5, E9.5, and E10.5, direction of looping is normal but the ventricular loop is rotated clockwise and displaced to the right
• heart appears displaced in relation to the head but is oriented normally in relation to the forelimb buds
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• seen in all homozygotes
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• ventricular septal defect
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| N |
• despite abnormalities in aortic arch patterning, neural crest cell migration appears normal, the cranial and dorsal root ganglia are normal in size and position, and no defects in left-right patterning are detected
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• at headfold stage, the embryo length to width ratio is reduced similar to that observed in Dvl1tm1Awb Dvl2tm1Awb homozygotes
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• incomplete axial rotation resulting in misalignment of the head and trunk
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• the notochord is broader
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| N |
• despite abnormalities in aortic arch patterning, neural crest cell migration appears normal and the cranial and dorsal root ganglia are normal in size and position
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• increased rows of hair cells within the third of the cochlea nearest the apex
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• 70% of inner hair cell bundles are misoriented
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• misorientation of stereociliary bundles at E18.5, more severe in the medial region than the base with approximately 95% misoriented in the two outer rows of outer hair cells
(J:100861)
• a significant proportion of bundles in all 3 layers are misoriented
(J:132697)
• vertices are randomly oriented with rotation angles of 40 - 180 degrees
(J:132697)
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• reduced cervical flexure
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Background Sensitivity: neural tube closure delay is less severe (1.2-somites delay) on the C3H/HeH background than on the mixed CBA and LPT/Le background (1.9-somites delay)
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• Background Sensitivity: looped tail phenotype becomes less penetrant on the C3H/HeH background, seen in 55% of mutants
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• Background Sensitivity: neural tube closure delay is less severe (1.2-somites delay) on the C3H/HeH background than on the mixed CBA and LPT/Le background (1.9-somites delay)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• seen in less than 10% of females
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• seen in less than 10% of females
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• Background Sensitivity: head wobble seen in mice on an LPT/LeJ background is lost in mice descended from KF Stein's albino stock
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• reduction if the frequency of forepaw vibrations
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• mice will often fall on their sides when running
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• mice display head rocking or wobbling that in some cases tends to choreic activity
(J:13059)
• choreatic movement of the head
(J:133042)
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• all mice with a marked degree of head shaking also show brain abnormalities
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• absence of tail rattling behavior
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• decrease in the frequency of wire mesh climbing
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• decreased frequency of rearing which involves shaking movements of the forepart of the body
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| N |
• Background Sensitivity: no ventricle abnormalities are detected in mice descended from KF Stein's albino stock unlike mice on an LPT/LeJ background
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• in 5% of mice
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• stereociliary bundles in apical regions are rotated compared to in wild-type mice
(J:142392)
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• large ventriculus impar
• however, the third and fourth ventricles appear unaffected
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• seen in 7 of 9 mice examined although sometimes only unilaterally
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• appears to be reduced in some places
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• slightly deformed at the medial margin and in the septal area with the nucleus lateralis septi clearly malformed
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• somewhat deformed and caudally displaced
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• partial penetrance of loops in the tail
(J:13059)
• variable degree of contortion of the tail ranging from extreme pretzel-like twists to minor angular crooks or curves
(J:13059)
• in 21 of 28 mice
(J:201925)
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• about one third of females lack a vaginal opening
(J:13059)
(J:162640)
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• frequent bifurcation of the xiphoid process, extending beyond the cartilaginous tip, is seen
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| N |
• despite abnormal head movements, mice are not deaf
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• stereociliary bundles in apical regions are rotated compared to in wild-type mice
(J:142392)
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• in 5% of mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 54% of embryos develop craniorachischisis
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• 54% of embryos develop craniorachischisis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• when cultured starting at E8.5 more embryos with open neural tubes are detected suggesting an increase in susceptibility to failure of neural tube closure in stressful conditions
• however, initiation of closure of the cranial neural tube at the midbrain/forebrain boundary is similar to wild-type
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• explants of E8.5 embryos show a delay in closure of about 4 - 6 hrs
• explants of E9.5 and E10.5 embryos show a delay of posterior neuropore closure
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• when cultured starting at E8.5 more embryos with open neural tubes are detected suggesting an increase in susceptibility to failure of neural tube closure in stressful conditions
• however, initiation of closure of the cranial neural tube at the midbrain/forebrain boundary is similar to wild-type
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• explants of E8.5 embryos show a delay in closure of about 4 - 6 hrs
• explants of E9.5 and E10.5 embryos show a delay of posterior neuropore closure
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at the 6 to 7 somite stage the posterior length to width ratio is significantly decreased compared to controls
• however, the whole embryo length to width ratio is not significantly different from controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Background Sensitivity: neural tube closure delay is more severe on this background (1.9-somites delay) than on the C3H/HeH background (1.2-somites delay)
|
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• Background Sensitivity: looped tail phenotype is more penetrant, seen in 90% of mutants, than on the C3H/HeH background in which 55% of mutants have a looped
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• Background Sensitivity: neural tube closure delay is more severe on this background (1.9-somites delay) than on the C3H/HeH background (1.2-somites delay)
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal stereocilia orientation at E18.5 and in inner ears cultured from E14.5 for 6 days
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• tails are kinked or looped
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• Background Sensitivity: unlike mice descended from KF Stein's albino stock, head wobble is seen
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• neural tube remains open at 8- to 9-somite stage
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• distortions in the septal area
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• occasionally slightly enlarged
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• usually bilaterally enlarged and distorted although the abnormality may be unilateral
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• distortions to the overall shape
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• neural tube remains open at 8- to 9-somite stage
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in 2 of 13 embryos
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• in 10 of 13 embryos
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• bundle orientation of OHC2 and OHC3 at the apical regions of the organ of Corti is severely affected
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• in 3 of 5 embryos with craniorachischisis
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• in 2 of 13 embryos
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• in 10 of 13 embryos
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• bundle orientation of OHC2 and OHC3 at the apical regions of the organ of Corti is severely affected
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Vestibular hair cell planar polarity defects in Vangl2tm1.2Mdea/Vangl2tm1.2Mdea and Vangl2tm1.2Mdea/Vangl2Lp mice
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• more numerous and disorganized cells compared with Vangl2tm1.2Mdea homozygotes
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• reverse orientation
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• abnormal orientation in the mid to last rows
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• extra rows
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• more numerous and disorganized cells in more fields compared with Vangl2tm1.2Mdea homozygotes
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• more numerous and disorganized cells compared with Vangl2tm1.2Mdea homozygotes
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• reverse orientation
|
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• abnormal orientation in the mid to last rows
|
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• extra rows
|
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• more numerous and disorganized cells in more fields compared with Vangl2tm1.2Mdea homozygotes
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• penetrance is reduced compared to Dact1 single mutants
|
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• penetrance is reduced compared to Dact1 single mutants
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• penetrance is reduced compared to Dact1 single mutants
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• penetrance is reduced compared to Dact1 single mutants
|
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• penetrance is reduced compared to Dact1 single mutants
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• penetrance is reduced compared to Dact1 single mutants
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• penetrance is reduced compared to Dact1 single mutants
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• penetrance of the loop tail phenotype is decreased to less than 20% compared to greater than 80% in Vangl2 single heterozygotes
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• similar to the phenotype in Vangl2 single homozygotes
|
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• similar to the phenotype in Vangl2 single homozygotes
|
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• penetrance of the loop tail phenotype is decreased to less than 65% compared to greater than 80% in Vangl2 single heterozygotes
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• rightward skewing of the embryo, with shortening of the right-hand size compared with the left, suggesting a defect in embryo turning
|
|
• 100% of embryos exhibit craniorachischisis, occurring usually as an isolated defect (in 89% of mutants) but sometimes associated with an abdominal wall defect (in 11% of mutants)
|
|
• abdominal wall defect in 11% of mutants, which is likely to be omphalocele/exomphalos
|
|
• 100% of embryos exhibit craniorachischisis, occurring usually as an isolated defect (in 89% of mutants) but sometimes associated with an abdominal wall defect (in 11% of mutants)
|
|
• 3 of 5 mutants fail to close eyelids at E16.5, while others show partial eyelid closure
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| neural tube defect | DOID:0080074 |
OMIM:301410 OMIM:601634 |
J:216413 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• skewed body axis in some mutants
|
|
• 81% of mutants exhibit craniorachischisis, most often isolated (in 50% of mutants) but sometimes associated with abdominal wall defect (in 31% of mutants) and a skewed body axis
|
|
• 3% of mutants exhibit only an abdominal wall defect while 31% exhibit both abdominal wall defect and craniorachischisis
|
|
• 6% of mutants exhibit a looped tail
|
|
• 13% of mutants are viable postnatally
|
|
• 81% of mutants exhibit craniorachischisis, most often isolated (in 50% of mutants) but sometimes associated with abdominal wall defect (in 31% of mutants) and a skewed body axis
|
|
• 3% of mutants exhibit exencephaly
|
|
• all mutants exhibit failure of eyelid closure at E16.5; all these have craniorachischisis
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| neural tube defect | DOID:0080074 |
OMIM:301410 OMIM:601634 |
J:216413 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 2 of 3 mutants exhibit craniorachischisis
|
|
• 1 of 3 mice exhibits hindbrain exencephaly and a tail defect
|
|
• 2 of 3 mutants exhibit craniorachischisis
|
|
• 1 of 3 mice exhibits hindbrain exencephaly and a tail defect
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 54% of embryos develop craniorachischisis
|
|
• the mice that do not develop craniorachischisis exhibit a looped tail
|
|
• 54% of embryos develop craniorachischisis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 13% of mice exhibit spina bifida
|
|
• 13% of mice exhibit spina bifida
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit an anterior-posterior elongation defect that is enhanced in the trunk relative to that observed in Sfrp1tm1Aksh/Sfrp1tm1Aksh Sfrp2tm1Aksh/Sfrp2tm1Aksh Sfrp5tm1Aksh/Sfrp5+ mice
• at late head-fold stage, mice exhibit abnormal convergence and extension
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 62% of mice exhibit spina bifida
|
|
• 62% of mice exhibit spina bifida
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 37% of embryos (n=18) display cardiac defects
|
|
• most defects are VSDs
|
|
• in 53% of embryos (n=17)
|
|
• in 53% of embryos (n=17)
|
|
• in 53% of embryos (n=17)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 50% of embryos (n=6) display cardiac defects compared to 0% of embryos heterozygous for either mutation alone
|
|
• most defects are VSDs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 35% of embryos (n=20) display cardiac defects
|
|
• most defects are VSDs
|
|
• in 4% of embryos (n=25)
|
|
• in 4% of embryos (n=25)
|
|
• in 4% of embryos (n=25)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• patterning and polarity defects
|
|
• coordinated orientation of the outer-most row of hair cells is disrupted
• 29.2% of the 4th row of hair cells have an orientation deviation of 30 degrees or larger from the planar cell polarity axis compared to only 0.9% of hairs in wild-type controls
|
|
|
• all females are sterile compared to less than 10% of mice heterozygous for Vangl2Lp alone
|
|
• patterning and polarity defects
|
|
• coordinated orientation of the outer-most row of hair cells is disrupted
• 29.2% of the 4th row of hair cells have an orientation deviation of 30 degrees or larger from the planar cell polarity axis compared to only 0.9% of hairs in wild-type controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• arrest at approximately E9.5
|
|
• fail to undergo turning
|
|
• at approximately E9.5
|
|
• shorter at E9.5
|
|
• open along the entire axis of the embryo at E9.5
|
|
• shorter at E9.5
|
|
• open along the entire axis of the embryo at E9.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• hair cell stereociliary bundle morphology is mostly unaffected
|
|
• spina bifida is seen in 94% of double heterozygotes
|
|
• spina bifida is seen in 94% of double heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• inner hair cells are misoriented compared to in wild-type mice
|
|
• outer hair cells are misoriented compared to in wild-type mice
|
|
• compared with Vangl1Gt(XL802)Byg/Vangl1Gt(XL802)Byg Vangl2tm1.2Yy/Vangl2+
|
|
• inner hair cells are misoriented compared to in wild-type mice
|
|
• outer hair cells are misoriented compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increase in the severity of cystic tubules compared to mice homozygous for Fat4tm1.1Hmc alone
|
|
• increase in the severity of cystic tubules compared to mice homozygous for Fat4tm1.1Hmc alone
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• orientation is significantly disrupted
• organization of hair cells is normal
|
|
• disruptions are most severe for inner hair cells
|
|
• orientation is significantly disrupted
• organization of hair cells is normal
|
|
• disruptions are most severe for inner hair cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Background Sensitivity: defects seen in the midbrain region at E13.5
|
| N |
• sensory hair cells in the cochlea are normal
|
|
• Background Sensitivity: defects seen in the midbrain region at E13.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• Background Sensitivity: no defects in neural tube closure are seen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Vangl1Gt(XL802)Byg/Vangl1+ Vangl2Lp/Vangl2+ and Vangl2Lp/Vangl2Lp embryos exhibit aberrant right subclavian artery
|
• fewer than expected double heterozygotes are found at weaning (20% rather than the expected 50%) given the presence of craniorachischisis late embryonic lethality is probably the cause of the distorted ratio
|
|
• seen in over 60% of double heterozygotes at E13.5 - E18.5
• phenotype is as severe as in mice homozygous for Vangl2Lp alone
• no obvious neural tube defects are seen in surviving mice
|
|
• profoundly distorted
|
|
• 20% of inner hair cell bundles are misoriented
|
|
• some bundles in all 3 layers are misoriented especially at the apical turn (over 50% of bundles in OHC1, 65% in OHC2, over 80% in OHC3)
• vertices are randomly oriented with rotation angles of 40 - 180 degrees
|
| N |
• unlike mice homozygous for Vangl2Lp alone, no outflow tract abnormalities are detected in double heterozygotes
|
|
• at E14.5, the right subclavian artery is positioned dorsal to the esophagus
|
|
• reduced in size at E18.5 in mice displaying craniorachischisis
|
|
• profoundly distorted
|
|
• 20% of inner hair cell bundles are misoriented
|
|
• some bundles in all 3 layers are misoriented especially at the apical turn (over 50% of bundles in OHC1, 65% in OHC2, over 80% in OHC3)
• vertices are randomly oriented with rotation angles of 40 - 180 degrees
|
|
• seen in over 60% of double heterozygotes at E13.5 - E18.5
• phenotype is as severe as in mice homozygous for Vangl2Lp alone
• no obvious neural tube defects are seen in surviving mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| neural tube defect | DOID:0080074 |
OMIM:301410 OMIM:601634 |
J:132697 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in 4 of 7 mice, more common in the rostral neural tube
|
|
• muscular and/or membranous in mice with neural tube defects
|
|
• in 4 of 7 mice, more common in the rostral neural tube
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in all mice, more common in the caudal neural tube
|
|
• cochlear hair cell defects (hair cell number and outer hair cell row 3 orientation) are modestly more severe than in Vangl2Lp heterozygotes
|
|
• most severe in outer hair cell row 3
|
|
• cochlear hair cell defects (hair cell number and outer hair cell row 3 orientation) are modestly more severe than in Vangl2Lp heterozygotes
|
|
• most severe in outer hair cell row 3
|
|
• muscular and/or membranous in mice with neural tube defects
|
|
• in all mice, more common in the caudal neural tube
|
|
• in 50% of mice
|
|
• in 50% of mice
|
|
• in 50% of mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in 12 of 27 mice, more common in the rostral neural tube
|
|
• muscular and/or membranous in mice with neural tube defects
|
|
• in 12 of 27 mice, more common in the rostral neural tube
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• open neural tubes in the midbrain region
• observable by E9.5 and occurring with 20% penetrance, this phenotype was not observed in lone C101 homozygotes or lone Lp heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in double homozygotes there is a rostral extension of the neural tube defect such that embryos display an open neural tube from the midbrain to the tail in 36% of the mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all double heterozygotes die by E13.5
|
|
• some outer hair cell stereociliary hair bundles have a flattened shape
|
|
• some outer hair cell stereociliary hair bundles are misoriented
|
|
• some outer hair cell stereociliary hair bundles have a flattened shape
|
|
• some outer hair cell stereociliary hair bundles are misoriented
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some mice develop similar neural tube defects as in Dvl3tm1Awb Vangl2Lp double heterozygotes
|
|
• in 6 of 16 mice
|
|
• some mice exhibit a loss of outer hair cell rows compared to in wild-type mice along 5% to 20% of the cochlear length
|
|
• some mice exhibit additional rows of outer and inner cells in the apical region of the cochlea compared to in wild-type mice
|
|
• the orientation of many cochlear hair cell stereociliary bundles is disrupted in the base and middle of the cochlear ducts
• mice with neural tube defects exhibit more severe orientation defects than in mice with normal neural tube closure
• stereociliary bundles in apical regions are rotated compared to in wild-type mice
|
|
• mice exhibit conotruncal defects
|
|
• some mice exhibit a loss of outer hair cell rows compared to in wild-type mice along 5% to 20% of the cochlear length
|
|
• some mice exhibit additional rows of outer and inner cells in the apical region of the cochlea compared to in wild-type mice
|
|
• the orientation of many cochlear hair cell stereociliary bundles is disrupted in the base and middle of the cochlear ducts
• mice with neural tube defects exhibit more severe orientation defects than in mice with normal neural tube closure
• stereociliary bundles in apical regions are rotated compared to in wild-type mice
|
|
• in mice with neural tube defects
|
|
• some mice develop similar neural tube defects as in Dvl3tm1Awb Vangl2Lp double heterozygotes
|
|
• in 6 of 16 mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some mice develop neural tube abnormalities such as craniorachischisis and exencephaly
|
|
• some mice develop defects in rostral neural tube closure
|
|
• in 5 of 22 mice
|
|
• some mice exhibit a loss of outer hair cell rows compared to in wild-type mice along 5% to 20% of the cochlear length
|
|
• some mice exhibit additional rows of outer and inner cells in the apical region of the cochlea compared to in wild-type mice
|
|
• the orientation of cochlear hair cell stereociliary bundles in mice with neural tube defects is disrupted in the base and middle of the cochlear ducts
• stereociliary bundles in apical regions are rotated compared to in wild-type mice
|
|
• in 2 of 22 mice
|
| N |
• hearts develop normally
|
|
• some mice exhibit a loss of outer hair cell rows compared to in wild-type mice along 5% to 20% of the cochlear length
|
|
• some mice exhibit additional rows of outer and inner cells in the apical region of the cochlea compared to in wild-type mice
|
|
• the orientation of cochlear hair cell stereociliary bundles in mice with neural tube defects is disrupted in the base and middle of the cochlear ducts
• stereociliary bundles in apical regions are rotated compared to in wild-type mice
|
|
• in mice with neural tube defects
|
|
• some mice develop neural tube abnormalities such as craniorachischisis and exencephaly
|
|
• some mice develop defects in rostral neural tube closure
|
|
• in 5 of 22 mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• genitourinary defects in 2 of 15 mice compared with 4 of 11 Sestd1tm1.1Bnrc homozygotes
|
|
• in 1 of 15 mice
|
|
• in 6 of 15 mice
|
|
• genitourinary defects in 2 of 15 mice compared with 4 of 11 Sestd1tm1.1Bnrc homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• severe reduction in the embryo length to width ratio is observed similar to in Dvl1tm1Awb Dvl2tm1Awb Vangl2Lp triple homozygotes
|
|
• similar to that observed in Dvl1tm1Awb Dvl2tm1Awb Vangl2Lp triple homozygotes
|
|
• shorter, wider chochlear ducts
|
|
• increased rows of hair cells within the third of the cochlea nearest the apex
|
|
• misorientation of stereociliary bundles at E18.5
|
|
• occasionally misaligned inner hair cells are obverse
|
|
• similar to that observed in Dvl1tm1Awb Dvl2tm1Awb Vangl2Lp triple homozygotes
|
|
• increased rows of hair cells within the third of the cochlea nearest the apex
|
|
• misorientation of stereociliary bundles at E18.5
|
|
• occasionally misaligned inner hair cells are obverse
|
|
• no mice are recovered at birth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no mice are recovered at birth
|
|
• similar to that observed in Dvl1tm1Awb Dvl2tm1Awb Vangl2Lp triple homozygotes
|
|
• similar to that observed in Dvl1tm1Awb Dvl2tm1Awb Vangl2Lp triple homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 7% of double heterozygotes die by E13.5
|
|
• some outer hair cell stereociliary hair bundles have a flattened shape
|
|
• some outer hair cell stereociliary hair bundles are misoriented
|
|
• some outer hair cell stereociliary hair bundles have a flattened shape
|
|
• some outer hair cell stereociliary hair bundles are misoriented
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 23% exhibit spina bifida or craniorachischisis
|
|
• 23% exhibit spina bifida or craniorachischisis
|
|
• 23% exhibit spina bifida or craniorachischisis
|
|
• 23% exhibit spina bifida or craniorachischisis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• over 50% of mice die between late embryogenesis and four weeks of age
|
|
• over 50% of mice die between late embryogenesis and four weeks of age
|
|
• in 68% of mice
|
|
• in 68% of mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• low frequency as in Vangl2Lp heterozygotes
|
|
• low frequency as in Vangl2Lp heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• shorter than in Vangl2Lp homozygotes
|
|
• precocious hindlimb induction
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit meningomyelocele
|
|
• at E16.5 and E18.5 mice with meningomyelocele display increased astrocyte staining compared to in wild-type mice
|
|
• in mice with meningomyelocele, the dorsal region of the neural tube lays laterally to the ventral horn and the dorsal white matter is moved into a ventrolateral position unlike in wild-type mice
• at E16.5, the number of neuronal cells in the meningomyelocele placode is decreased compared to in wild-type mice
|
|
• mice exhibit meningomyelocele with hypotonic hindlimbs with spontaneous and extensive movement of the hip and knee joints but only slight movement at the ankle joints
• mice do not display coordination between fore- and hindlimbs
• mice occasionally exhibit plantar steps that demonstrate the ability to support their body weight
|
|
• mice with meningomyelocele exhibit reduced fetal weight
|
|
• mice exhibit meningomyelocele
|
|
• mice exhibit meningomyelocele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• everely affected in OHC2 and OHC3 layers at all three regions analyzed except for OHC3 in the middle region of the organ of Corti
|
|
• kinky/looped tail in most mice
|
|
• kinky/looped tail in most mice
|
|
• in some mice unlike single heterozygotes
|
|
• in some mice unlike single heterozygotes
|
|
• everely affected in OHC2 and OHC3 layers at all three regions analyzed except for OHC3 in the middle region of the organ of Corti
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• show either craniorachischisis or loop tail
|
|
• show either craniorachischisis or loop tail
|
|
• show either craniorachischisis or loop tail
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 29 of 54 double heterozygotes exhibit craniorachisichisis and the remainder had either spina bifida or a looped tail
|
|
• in a small minority of double heterozygotes
|
|
• 29 of 54 double heterozygotes exhibit craniorachisichisis and the remainder had either spina bifida or a looped tail
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• nuclei in the epiblast are more spherical and randomly aligned along the apical basal axis
• expression analysis indicates that apical-basal cell polarity is disrupted similar to the phenotype of single homozygous Prickle1 mutant mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• arrest at approximately E9.5
|
|
• fail to undergo turning
|
|
• at E8.0 - E8.5 expression analysis indicates randomized left-right axis patterning
|
|
• at approximately E9.5
|
|
• shorter at E9.5
|
|
• open along the entire axis of the embryo at E9.5
|
|
• midline is shorter and wider at the 1 to 4 somite stage compared to either single mutant
• threefold shorter and wider compared to wild-type controls, twofold shorter and wider compared to Vangl2Lp single mutants
• change in size is not due to changes in cell shape
|
|
• expression analysis indicates many node cells lack posterior polarization
|
|
• cilia are normal in length but do not point uniformly to the posterior and their position on the cell is more variable than in controls
|
|
• significantly reduced length to width ratio compared to either single mutant
|
|
• in 2 of 6 embryos at E9.5
|
|
• a linear heart tube is seen at E9.5 in 1 of 6 embryos
|
|
• shorter at E9.5
|
|
• at E8.0 - E8.5 expression analysis indicates randomized left-right axis patterning
|
|
• open along the entire axis of the embryo at E9.5
|
|
• cilia are normal in length but do not point uniformly to the posterior and their position on the cell is more variable than in controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E18.5 the polarized subcellular distribution of Dvl2 driven GFP expression in the differentiating organ of Corti is disrupted
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/16/2024 MGI 6.23 |
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