Mouse Genome Informatics
hm1
    Nodaltm1Rob/Nodaltm1Rob
involves: 129S/SvEv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• phenotype is stated to be identical to that of NodalTg(MPSVNeo)413.dRob homozygotes; however no data are presented in J:32935

embryogenesis

growth/size


Mouse Genome Informatics
ht2
    Nodaltm1Rob/Nodal+
involves: 129S/SvEv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype


Mouse Genome Informatics
ht3
    Nodaltm1Rob/Nodal+
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
EuPh (J:165965)

homeostasis/metabolism

other phenotype
EuPh (J:165965)


Mouse Genome Informatics
ht4
    Nodaltm1Rob/Nodaltm2Rob
involves: 129S/SvEv * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• in some mice
• severely affected mice exhibit a decrease in midline tissue compared with wild-type mice due to abnormal gastrulation movements
• at E8.5, mice exhibit a reduction in anterior neural tissues compared with wild-type mice
• in some mice
• fused somites
• constriction at the boundary in 40% of mice at E6.5
• at E6.5, 40% of embryos are abnormal with thickened patch of visceral endoderm characteristic of the anterior visceral endoderm

cardiovascular system
• in some mice


Mouse Genome Informatics
cn5
    Meox2tm1(cre)Sor/Meox2+
Nodaltm1Rob/Nodaltm5Rob

involves: 129S/SvEv * 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• development was variable
• fail to rotate their proximal distal axis
• variable amounts of anterior truncation at E6.5
• in severe cases an elongate morphology at E6.5
• profound anterior truncations by E8.5
• embryos occasionally protrude outside the yolk sac at E6.5


Mouse Genome Informatics
cn6
    Nodaltm1Rob/Nodaltm5Rob
Tg(Sox2-cre)1Amc/0

involves: 129S/SvEv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• lacked mesoderm at gastrulation
• thickened distal visceral endoderm


Mouse Genome Informatics
cn7
    Nodaltm1Rob/Nodal+
Tg(Sox2-cre)1Amc/0
Tgif1tm1Caw/Tgif1tm1Caw
Tgif2tm1Dwot/Tgif2tm1Dwot

involves: 129S/SVEv * C57BL/6 * C57BL/6J * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• expression analysis suggests there are some mild defects in left right patterning

cardiovascular system
N
• unlike in double null mice wild-type for Nodal, heart looping morphogenesis is normal (J:157256)


Mouse Genome Informatics
cn8
    Eomestm1Rob/Eomes+
Nodaltm1Rob/Nodal+
Tg(Sox2-cre)1Amc/0

involves: 129S/SvEv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• severely affected embryos are not recovered

embryogenesis
• embryos with anterior axis truncations are recovered at low frequency


Mouse Genome Informatics
cx9
    Acvr1ctm1Cfi/Acvr1c+
Gdf1tm1Sjl/Gdf1+
Nodaltm1Rob/Nodal+

involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype


Mouse Genome Informatics
cx10
    Nodaltm1Rob/Nodal+
Tgif1tm1Dwot/Tgif1tm1Dwot
Tgif2tm1Dwot/Tgif2tm1Dwot

involves: 129/Sv * 129S/SvEv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
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 (J:157256)


Mouse Genome Informatics
cx11
    Acvr1btm1Enl/Acvr1b+
Gdf1tm1Sjl/Gdf1+
Nodaltm1Rob/Nodal+

involves: 129/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 3 of 19 mutants have a single forebrain vesicle

respiratory system
• 3 of 19 mutants have a fused nasal cavity

craniofacial
• 3 of 19 mutants have a fused nasal cavity

growth/size
• 3 of 19 mutants have a fused nasal cavity


Mouse Genome Informatics
cx12
    Acvr1ctm1Cfi/Acvr1ctm1Cfi
Nodaltm1Rob/Nodal+

involves: 129P2/OlaHsd * 129/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• expected numbers of compound mutants are detected at weaning (J:94135)


Mouse Genome Informatics
cx13
    Cer1tm1Bhr/Cer1tm1Bhr
Lefty1tm1Hmd/Lefty1tm1Hmd
Nodaltm1Rob/Nodal+

involves: 129P2/OlaHsd * 129S/SvEv * 129S7/SvEvBrd * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• all triple mutant embryos at 7.5 dpc show morphological defects similar to or less severe than Cer1 Lefty1 double mutants


Mouse Genome Informatics
cx14
    Lefty2tm1Hmd/Lefty2tm1Hmd
Nodaltm1Rob/Nodal+

involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6Cr
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

embryogenesis
• defects in embryogenesis due to a lack of Lefty2 are partially rescued although mice die in late gastrulation


Mouse Genome Informatics
cx15
    Nodaltm1Rob/Nodal+
Nogtm1Amc/Nogtm1Amc

involves: 129S/SvEv * 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
N
• no defects are detected in anterior midline tissues (J:161524)


Mouse Genome Informatics
cx16
    Foxa2tm1Jrt/Foxa2+
Nodaltm1Rob/Nodal+

involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• in embryos with loss of left-right asymmetry in Nodal expression the direction of turning is randomized
• seen in all embryos

growth/size
• in 7 of 10 mutants the positioning of the abdominal viscera and heart is abnormal


Mouse Genome Informatics
cx17
    Chrdtm1Emdr/Chrdtm1Emdr
Nodaltm1Rob/Nodal+

involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• in 14 of 19 mice with defects in anterior midline tissues

embryogenesis
• expression analysis indicates defects in patterning and function
• 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
• fused in 14 of 19 mice with defects in anterior midline tissues
• expression analysis indicates defects in patterning and function in the anterior most axial mesendoderm
• expression analysis indicates impairment in ADE specification

cardiovascular system
• cardiac laterality defects are seen in 5 mice

craniofacial
• fused in 14 of 19 mice with defects in anterior midline tissues


Mouse Genome Informatics
cx18
    Gdf1tm1Sjl/Gdf1tm1Sjl
Nodaltm1Rob/Nodal+

involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• fewer than expected mutants at E13.5

embryogenesis
• defects are seen in structures arising from the first but not the second branchial arch
• at E9.0, the first branchial arch is fused, lacking a midline division
• primitive streak elongation is normal but significant reduction in the number of axial mesendoderm cells is detected in about 50% of mutants
• the prechordal plate marker Gsc is significantly downregulated at the late headfold stage and the prechordal plate is absent in severely affected embryos
• fail to develop anterior neural folds
• anterior defects only
• absent at E8.5 in the most severely affected embryos
• at E9.0 expression of Shh, a marker of the notochord at this stage, is anteriorly truncated

craniofacial
• severely affected embryos lack jaws
• defects are seen in structures arising from the first but not the second branchial arch
• at E9.0, the first branchial arch is fused, lacking a midline division
• seen in 68% of embryos at E13.5, associated with holoprosencephaly
• severely affected embryos lack the entire tongue while mildly affected embryos lack the distal portion of the tongue
• hypomorphic nasal septum resulting in a fused nasal cavity

nervous system
• anterior defects only
• seen in 68% of embryos at E13.5, associated with gross rostral truncation and cleft lip
• thickening of the diencephalon seen in embryos with holoprosencephaly
• a recessed third ventricle that fails to expand ventrally is seen in embryos with holoprosencephaly

digestive/alimentary system
• severely affected embryos lack the entire tongue while mildly affected embryos lack the distal portion of the tongue
• at E9.0, in most embryos the foregut does not reach into the center of the first branchial arch unlike in wild-type mice

respiratory system
• hypomorphic nasal septum resulting in a fused nasal cavity

skeleton
• severely affected embryos lack jaws

growth/size
• seen in 68% of embryos at E13.5, associated with holoprosencephaly
• severely affected embryos lack the entire tongue while mildly affected embryos lack the distal portion of the tongue
• hypomorphic nasal septum resulting in a fused nasal cavity


Mouse Genome Informatics
cx19
    Acvr2atm1Hsch/Acvr2atm1Hsch
Nodaltm1Rob/Nodal+

involves: 129S/SvEv * 129S1/Sv * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• embryonic lethality although time not specified

embryogenesis
• over 60% show gastrulation defects

nervous system
• 4 of 13 embryos that developed beyond gastrulation have a reduced forebrain

vision/eye
• 6 of 8 newborns display cyclopia

growth/size
• 6 of 8 newborns show truncation of rostral head structures


Mouse Genome Informatics
cx20
    Nodaltm1Rob/Nodaltm2Rob
Trim33tm1.2Los/Trim33tm1.2Los

involves: 129S/SvEv * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
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 (J:163858)


Mouse Genome Informatics
cx21
    Nodaltm1Rob/Nodal+
Trim33tm1.2Los/Trim33tm1.2Los

involves: 129S/SvEv * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
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 (J:163858)


Mouse Genome Informatics
cx22
    Smad2tm1Enl/Smad2+
Nodaltm1Rob/Nodal+

involves: 129S/SvEv * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• at E9.5 11 of 20 embryos had gastrulation defects similar to those in Smad2 single heterozygotes
• 3 of 20 turn in the opposite direction compared to wild-type mice
• in affected embryos lateral plate mesoderm is restricted to the posterior region
• 32% (8 of 25) have defects in left-right patterning
• in the most severe cases the rostral head and eyes are truncated

cardiovascular system
• 3 of 20 have abnormal heart looping
• most common cardiac defect in embryos with left-right patterning abnormalities

growth/size
• seen in 6 of 25 embryos, these mice also have transposition of the great arteries

craniofacial
• at E15.5 - E17.5 severe craniofacial defects are seen in 14 of 25 mutants

vision/eye
• present at E15.5 - E17.5 in 9 of 25

respiratory system
• seen in 6 of 25 embryos, these mice also have transposition of the great arteries


Mouse Genome Informatics
cx23
    Drap1tm1Mms/Drap1tm1Mms
Nodaltm1Rob/Nodal+

involves: 129S/SvEv * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutant embryos die by E9.5

embryogenesis
• mutant embryos are partially rescued from the mesoderm defects observed in Drap1tm1Mms homozygotes, but are still unable to complete gastrulation
• at E7.5 and E8.25, mutant embryos display a characteristic proximal bulge in the caudal primitive streak


Mouse Genome Informatics
cx24
    Eomestm1.1Rob/Eomes+
Nodaltm1Rob/Nodal+

involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• AVE is correctly induced but fails to migrate anteriorly
• heart patterning abnormalities are observed by E9.5 due to loss of midline structures
• at E8.5, development of the node is severely disturbed in a subset of mutants
• complete node duplications are observed in some mutants
• the most severely affected double heterozygotes show abnormalities around E7 and fail to form a primitive streak
• embryos lack visible germ layers
• left-right patterning abnormalities are observed by E9.5 due to loss of midline structures
• floor plate expansion results in increased spacing between somite rows at E9.5
• by E9.5, mutants lack head structures rostral to the otic placodes
• in the most severely affected embryos, relatively complete duplications of the posterior body axis are observed, including extra somite rows
• node abnormalities result in expansion of the floor plate of the neural tube
• node duplications are accompanied by formation of an accessory notochord
• addition rows of somites are observed in the most severely affected embryos
• by late gastrulation stages, embryos are grossly disorganized
• the most severely affected embryos develop pronounced constrictions between the embryonic and extraembryonic regions of the conceptus
• embryos frequently show tissue accumulation within the amniotic cavity

nervous system
• node abnormalities result in expansion of the floor plate of the neural tube

cellular
• AVE is correctly induced but fails to migrate anteriorly


Mouse Genome Informatics
cx25
    Cer1tm1Bhr/Cer1tm1Bhr
Lefty1tm1Sla/Lefty1tm1Sla
Nodaltm1Rob/Nodal+

involves: 129S/SvEv * 129S7/SvEvBrd * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• all triple mutant embryos at 7.5 dpc show morphological defects similar to or less severe than Cer1 Lefty1 double mutants


Mouse Genome Informatics
cx26
    Col2a1tm1.1Ksec/Col2a1tm1.1Ksec
Nodaltm1Rob/Nodal+

involves: 129S/SvEv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• the frequency of head abnormalities is not significantly different from Col2a1tm1.1Ksec single homozygotes


Mouse Genome Informatics
cx27
    Col2a1tm1.1Ksec/Col2a1+
Nodaltm1Rob/Nodal+

involves: 129S/SvEv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• the frequency of head abnormalities is not significantly different from Col2a1tm1.1Ksec single heterozygotes