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Allele Symbol Allele Name Allele ID |
Nodaltm1Rob targeted mutation 1, Elizabeth J Robertson MGI:2180793 |
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| Summary |
28 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• phenotype is stated to be identical to that of NodalTg(MPSVNeo)413.dRob homozygotes; however no data are presented in J:32935
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in some mice
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• severely affected mice exhibit a decrease in midline tissue compared with wild-type mice due to abnormal gastrulation movements
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• at E8.5, mice exhibit a reduction in anterior neural tissues compared with wild-type mice
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• in some mice
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• in some mice
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• fused somites
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• constriction at the boundary in 40% of mice at E6.5
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• at E6.5, 40% of embryos are abnormal with thickened patch of visceral endoderm characteristic of the anterior visceral endoderm
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• in some mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• development was variable
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• fail to rotate their proximal distal axis
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• variable amounts of anterior truncation at E6.5
• in severe cases an elongate morphology at E6.5
• profound anterior truncations by E8.5
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• embryos occasionally protrude outside the yolk sac at E6.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• lacked mesoderm at gastrulation
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• thickened distal visceral endoderm
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduced Nodal levels partially rescues ventral neurepithelium morphogenesis observed in double mutants with disorganized neuroepithelium
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• reduced Nodal levels partially rescues ventral forebrain morphology observed in double mutants with less disorganization and larger size
• however, forebrain cell proliferation is restored
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• in mice that survive to E18.5
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• in two-thirds of mice
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• expression analysis suggests there are some mild defects in left right patterning
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• severe anterior truncation in a small proportion of mice
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• in 2 embryos with severe anterior truncation
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• reduced Nodal levels partially rescues ventral neurepithelium morphogenesis observed in double mutants with disorganized neuroepithelium
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• in 2 embryos with severe anterior truncation
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| N |
• unlike in double null mice wild-type for Nodal, heart looping morphogenesis is normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• severely affected embryos are not recovered
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• embryos with anterior axis truncations are recovered at low frequency
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 78% of embryos present with moderate anterior truncation in which variable amounts of forebrain and/or midbrain are retained
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all triple mutant embryos at 7.5 dpc show morphological defects similar to or less severe than Cer1 Lefty1 double mutants
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die during late gastrulation
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• defects in embryogenesis due to a lack of Lefty2 are partially rescued although mice die in late gastrulation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• expected numbers of compound mutants are detected at weaning
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in embryos with loss of left-right asymmetry in Nodal expression the direction of turning is randomized
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• seen in all embryos
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• in 7 of 10 mutants the positioning of the abdominal viscera and heart is abnormal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in 14 of 19 mice with defects in anterior midline tissues
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• expression analysis indicates defects in patterning and function in the anterior most axial mesendoderm
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• 23% (19 of 83) show defects in anterior midline tissues
• 14 of these 19 show holoprosencephaly in association with anterior body truncation and fused first pharyngeal arches
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• fused in 14 of 19 mice with defects in anterior midline tissues
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• expression analysis indicates impairment in ADE specification
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• expression analysis indicates defects in patterning and function
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• cardiac laterality defects are seen in 5 mice
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• fused in 14 of 19 mice with defects in anterior midline tissues
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| holoprosencephaly | DOID:4621 |
OMIM:PS236100 |
J:161524 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• fewer than expected mutants at E13.5
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• defects are seen in structures arising from the first but not the second branchial arch
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• at E9.0, the first branchial arch is fused, lacking a midline division
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• primitive streak elongation is normal but significant reduction in the number of axial mesendoderm cells is detected in about 50% of mutants
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• fail to develop anterior neural folds
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• anterior defects only
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• absent at E8.5 in the most severely affected embryos
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• at E9.0 expression of Shh, a marker of the notochord at this stage, is anteriorly truncated
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• the prechordal plate marker Gsc is significantly downregulated at the late headfold stage and the prechordal plate is absent in severely affected embryos
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• severely affected embryos lack jaws, as shown by the absence of mandibles in skeleton preparations
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• defects are seen in structures arising from the first but not the second branchial arch
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• at E9.0, the first branchial arch is fused, lacking a midline division
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• seen in 68% of embryos at E13.5, associated with holoprosencephaly
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• severely affected embryos lack the entire tongue while mildly affected embryos lack the distal portion of the tongue
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• hypomorphic nasal septum resulting in a fused nasal cavity
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• anterior defects only
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• seen in 68% of embryos at E13.5, associated with gross rostral truncation and cleft lip
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• thickening of the diencephalon seen in embryos with holoprosencephaly
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• a recessed third ventricle that fails to expand ventrally is seen in embryos with holoprosencephaly
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• severely affected embryos lack the entire tongue while mildly affected embryos lack the distal portion of the tongue
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• at E9.0, in most embryos the foregut does not reach into the center of the first branchial arch unlike in wild-type mice
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• hypomorphic nasal septum resulting in a fused nasal cavity
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• severely affected embryos lack jaws, as shown by the absence of mandibles in skeleton preparations
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• seen in 68% of embryos at E13.5, associated with holoprosencephaly
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• severely affected embryos lack the entire tongue while mildly affected embryos lack the distal portion of the tongue
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• hypomorphic nasal septum resulting in a fused nasal cavity
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• embryonic lethality although time not specified
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• over 60% show gastrulation defects
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• 4 of 13 embryos that developed beyond gastrulation have a reduced forebrain
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• 6 of 8 newborns show truncation of rostral head structures
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• at E6.25 decrease in Nodal expression rescues patterning defects in the anterior visceral endoderm, extraembryonic ectoderm and mesoderm and the decrease in embryo size that are seen in Trim33 single homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• the decrease in Nodal expression rescues patterning defects in the extraembryonic ectoderm and mesoderm and the decrease in embryo size that are seen in Trim33 single homozygotes
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• expanded at E6.25
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E9.5 11 of 20 embryos had gastrulation defects similar to those in Smad2 single heterozygotes
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• 3 of 20 turn in the opposite direction compared to wild-type mice
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• 32% (8 of 25) have defects in left-right patterning
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• in the most severe cases the rostral head and eyes are truncated
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• in affected embryos lateral plate mesoderm is restricted to the posterior region
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• 3 of 20 have abnormal heart looping
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• most common cardiac defect in embryos with left-right patterning abnormalities
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• seen in 6 of 25 embryos, these mice also have transposition of the great arteries
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• at E15.5 - E17.5 severe craniofacial defects are seen in 14 of 25 mutants
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• seen in 6 of 25 embryos, these mice also have transposition of the great arteries
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutant embryos die by E9.5
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• mutant embryos are partially rescued from the mesoderm defects observed in Drap1tm1Mms homozygotes, but are still unable to complete gastrulation
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• at E7.5 and E8.25, mutant embryos display a characteristic proximal bulge in the caudal primitive streak
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• AVE is correctly induced but fails to migrate anteriorly
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• heart patterning abnormalities are observed by E9.5 due to loss of midline structures
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• embryos lack visible germ layers
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• left-right patterning abnormalities are observed by E9.5 due to loss of midline structures
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• floor plate expansion results in increased spacing between somite rows at E9.5
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• by E9.5, mutants lack head structures rostral to the otic placodes
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• in the most severely affected embryos, relatively complete duplications of the posterior body axis are observed, including extra somite rows
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• node abnormalities result in expansion of the floor plate of the neural tube
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• node duplications are accompanied by formation of an accessory notochord
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• at E8.5, development of the node is severely disturbed in a subset of mutants
• complete node duplications are observed in some mutants
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• the most severely affected double heterozygotes show abnormalities around E7 and fail to form a primitive streak
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• addition rows of somites are observed in the most severely affected embryos
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• by late gastrulation stages, embryos are grossly disorganized
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• the most severely affected embryos develop pronounced constrictions between the embryonic and extraembryonic regions of the conceptus
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• embryos frequently show tissue accumulation within the amniotic cavity
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• node abnormalities result in expansion of the floor plate of the neural tube
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• AVE is correctly induced but fails to migrate anteriorly
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all triple mutant embryos at 7.5 dpc show morphological defects similar to or less severe than Cer1 Lefty1 double mutants
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• the frequency of head abnormalities is not significantly different from Col2a1tm1.1Ksec single heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• unlike in double null mice wild-type for Nodal, the embryonic cavity has formed by E8.5 and a distinct AP axis is present
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• the frequency of head abnormalities is not significantly different from Col2a1tm1.1Ksec single homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in 1 of 41 mice between E10.5 and E12.5
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• 15 of 41 mice exhibit anterior truncations or a severe growth delay
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• single field
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• 15 of 41 mice exhibit anterior truncations or a severe growth delay
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• single field
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• single field
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• partial failure to separate eyes in 1 of 41 mice between E10.5 and E12.5
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• single field
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 3 of 19 mutants have a single forebrain vesicle
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• 3 of 19 mutants have a fused nasal cavity
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• 3 of 19 mutants have a fused nasal cavity
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• 3 of 19 mutants have a fused nasal cavity
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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 04/09/2024 MGI 6.23 |
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