cardiovascular system phenotype

• abnormal vitelline vasculature morphology
  • at E10.5, ~20% of homozygotes display a poorly vascularized yolk sac
  (MGI Ref ID J:47301)

• enlarged heart
  • at E10.5, ~20% of homozygotes have an enlarged heart cavity
  (MGI Ref ID J:47301)

• decreased cardiac muscle contractility
  • at E10.5, the heart contractions in mutant embryos appear to be weaker and less extensive than in wild-type embryos
  (MGI Ref ID J:47301)

• absent trabeculae carneae
  • at E10.5, homozygotes display significantly reduced ventricular trabeculation relative to wild-type
  (MGI Ref ID J:47301)

• pericardial effusion
  • at E10.5, homozygotes with an enlarged heart display pericardial effusion
  (MGI Ref ID J:47301)

embryo phenotype

• incomplete embryo turning
  • at E10.5, the most severe but still viable homozygotes display incomplete embryo turning
  (MGI Ref ID J:47301)

• embryonic growth retardation
  • at E10.5, the most severe but still viable homozygotes exhibit a developmental arrest at ~E8.5-E9.0
  (MGI Ref ID J:47301)

• incomplete somite formation
  • at E10.5, the most severe but still viable homozygotes contain only 12-16 somites
  (MGI Ref ID J:47301)
  • at this stage, mutant somites appear disorganized relative to wild-type
  (MGI Ref ID J:47301)

• decreased embryo size
  • at E10.5, homozygotes are much smaller than wild-type embryos and appear developmentally retarded
  (MGI Ref ID J:47301)

• abnormal vitelline vasculature morphology
  • at E10.5, ~20% of homozygotes display a poorly vascularized yolk sac
  (MGI Ref ID J:47301)

growth/size/body region phenotype

• embryonic growth retardation
  • at E10.5, the most severe but still viable homozygotes exhibit a developmental arrest at ~E8.5-E9.0
  (MGI Ref ID J:47301)

• decreased embryo size
  • at E10.5, homozygotes are much smaller than wild-type embryos and appear developmentally retarded
  (MGI Ref ID J:47301)

• enlarged heart
  • at E10.5, ~20% of homozygotes have an enlarged heart cavity
  (MGI Ref ID J:47301)

homeostasis/metabolism phenotype

• pericardial effusion
  • at E10.5, homozygotes with an enlarged heart display pericardial effusion
  (MGI Ref ID J:47301)

mortality/aging

• embryonic lethality during organogenesis, incomplete penetrance
  • at E10.5, 50% of homozygotes show either absence of heart beating or signs of reabsorption
  (MGI Ref ID J:47301)
  • homozygotes appear abnormal as early as E8.5 and die between E9.0 and E11.5
  (MGI Ref ID J:47301)

muscle phenotype

• absent trabeculae carneae
  • at E10.5, homozygotes display significantly reduced ventricular trabeculation relative to wild-type
  (MGI Ref ID J:47301)

• decreased cardiac muscle contractility
  • at E10.5, the heart contractions in mutant embryos appear to be weaker and less extensive than in wild-type embryos
  (MGI Ref ID J:47301)

cellular phenotype

• abnormal cell physiology
  • mutant MEFs display impaired retinoic acid receptor activity; in contrast, cAMP-dependent signaling appears unaffected
  (MGI Ref ID J:47301)

• decreased fibroblast proliferation
  • MEFs derived from 129/Sv inbred embryos exhibit more severe proliferative defects than 129/Sv x C57BL/6 MEFs
  (MGI Ref ID J:47301)
  • in addition to mutant embryos, isolated MEFs show a proliferation defect, growing much slower and for fewer generations relative to wild-type
  (MGI Ref ID J:47301)

• early cellular replicative senescence
  • unlike heterozygous and wild-type cells, homozygous mutant MEFs stop dividing after 3 to 4 cell generations
  (MGI Ref ID J:47301)

craniofacial phenotype

• abnormal facial morphology
  • in homozygotes, the facial structure is collapsed
  (MGI Ref ID J:47301)

nervous system phenotype

• open neural tube
  • late-arresting 129/Sv ¿ C57BL/6 mutant embryos show a severe open neural tube defect
  (MGI Ref ID J:47301)
  • the neural tube either fails to fuse from hindbrain to the forebrain region or remains completely open in severely affected embryos
  (MGI Ref ID J:47301)

• kinked neural tube
  • in homozygotes, the neural tube often shows a kinked morphology as opposed to the straight one found in wild-type
  (MGI Ref ID J:47301)

• exencephaly
  • the neural lumen (ventricle) is collapsed; abnormal masses of neural tissue are also observed
  (MGI Ref ID J:47301)
  • all 129/Sv ¿ C57BL/6 mutant embryos exhibit various degrees of exencephaly
  (MGI Ref ID J:47301)

vision/eye phenotype

• microphthalmia
  • the eyes of homozygous mutant embryos are smaller than those of wild-type embryos
  (MGI Ref ID J:47301)

embryo phenotype

• embryonic growth arrest
  • notably, 129/Sv ¿ C57BL/6 mutant embryos tend to arrest a day or so later than 129/Sv embryos
  (MGI Ref ID J:47301)

• open neural tube
  • late-arresting 129/Sv ¿ C57BL/6 mutant embryos show a severe open neural tube defect
  (MGI Ref ID J:47301)
  • the neural tube either fails to fuse from hindbrain to the forebrain region or remains completely open in severely affected embryos
  (MGI Ref ID J:47301)

• kinked neural tube
  • in homozygotes, the neural tube often shows a kinked morphology as opposed to the straight one found in wild-type
  (MGI Ref ID J:47301)

• decreased embryo size
  • late-arresting 129/Sv ¿ C57BL/6 mutant embryos are smaller than wild-type embryos but show no gross patterning defects
  (MGI Ref ID J:47301)

growth/size/body region phenotype

• abnormal facial morphology
  • in homozygotes, the facial structure is collapsed
  (MGI Ref ID J:47301)

• decreased embryo size
  • late-arresting 129/Sv ¿ C57BL/6 mutant embryos are smaller than wild-type embryos but show no gross patterning defects
  (MGI Ref ID J:47301)

mortality/aging

• embryonic lethality during organogenesis, complete penetrance
  • a few of 129/Sv x C57BL/6 embryos survive beyond E10.5, such mutants exhibit a less severe phenotype but die after E11.5
  (MGI Ref ID J:47301)

embryo phenotype

• decreased embryo size
  • at E10.5, heterozygotes with exencephaly are consistently smaller than wild-type embryos
  (MGI Ref ID J:47301)

• open neural tube
  • in heterozygotes, the neural tube defect is restricted to the anterior part of the hindbrain and the midbrain; the rest of the neural tube fuses normally
  (MGI Ref ID J:47301)
  • a fraction of heterozygotes exhibit defective neural tube closure
  (MGI Ref ID J:47301)
  • Background Sensitivity - considerably less lethality is observed on a mixed 129 x C57BL/6 background and none on an incipient congenic C57BL/6 background
  (MGI Ref ID J:47301)

nervous system phenotype

• open neural tube
  • Background Sensitivity - considerably less lethality is observed on a mixed 129 x C57BL/6 background and none on an incipient congenic C57BL/6 background
  (MGI Ref ID J:47301)
  • in heterozygotes, the neural tube defect is restricted to the anterior part of the hindbrain and the midbrain; the rest of the neural tube fuses normally
  (MGI Ref ID J:47301)
  • a fraction of heterozygotes exhibit defective neural tube closure
  (MGI Ref ID J:47301)

• exencephaly
  • the neural lumen (ventricle) is collapsed; abnormal masses of neural tissue are also observed
  (MGI Ref ID J:47301)
  • at E10.5, 6% of 129/Sv ¿ C57BL/6 and 19% of 129/Sv heterozygous mutant embryos display exencephaly
  (MGI Ref ID J:47301)

growth/size/body region phenotype

• decreased embryo size
  • at E10.5, heterozygotes with exencephaly are consistently smaller than wild-type embryos
  (MGI Ref ID J:47301)

mortality/aging

• embryonic lethality during organogenesis, incomplete penetrance
  • Background Sensitivity - considerably less lethality is observed on a mixed 129 x C57BL/6 background and none on an incipient congenic C57BL/6 background
  (MGI Ref ID J:47301)
  • at weaning, 55% fewer heterozygotes are obtained on a 129/Sv inbred genetic background
  (MGI Ref ID J:47301)
  • a fraction of heterozygotes die as early as at E10.5
  (MGI Ref ID J:47301)

mammalian phenotype

• hematopoietic system phenotype
  • Normal - at 12-18 months, heterozygotes exhibit neither splenomegaly nor hematopoietic differentiation defects
  (MGI Ref ID J:60630)

• neoplasm
  • Normal - at 10-21 months, heterozygotes show no increased incidence of hematologic malignancies compared with wild-type mice
  (MGI Ref ID J:60630)