Phenotypes associated with this allele
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad2tm1.1Epb mutation
(1 available);
any
Smad2 mutation
(50 available)
Smad3tm1Cxd mutation
(0 available);
any
Smad3 mutation
(18 available)
Speer6-ps1Tg(Alb-cre)21Mgn mutation
(6 available);
any
Speer6-ps1 mutation
(4 available)
|
|
|
liver/biliary system
|
N |
• mice exhibit normal postnatal liver and body growth and function
|
cellular
|
|
• only a few hepatocytes attach with atypical morphology after seeding
|
|
|
• isolated primary hepatocytes show decreased viability immediately upon isolation, prior to plating (<70% viable cells) compared to controls or other mutant genotypes
|
homeostasis/metabolism
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad2tm1.1Epb mutation
(1 available);
any
Smad2 mutation
(50 available)
Speer6-ps1Tg(Alb-cre)21Mgn mutation
(6 available);
any
Speer6-ps1 mutation
(4 available)
|
|
|
liver/biliary system
|
N |
• mice exhibit normal postnatal liver and body growth and function
|
|
|
• after attachment to culture dishes, hepatocytes are elongated with process formation and cell separation compared to wild-type cells which have a cobblestone epithelial morphology
|
|
|
• hepatocytes express much higher levels of vimentin (mesenchymal marker) compared to control or Smad3 mutant cells
|
|
|
• in culture, untreated cells exhibit ~3-fold greater proliferation compared to controls and Smad3 hepatocytes; after TGFbeta treatement, cells show reduced proliferation compared to controls
• in CCL4-injured livers, cell proliferation is higher at earlier time points than in controls or Smad3-deficient livers
|
cellular
|
|
• hepatocytes dedifferentiate spontaneously to acquire mesenchymal and promigratory features in culture
|
|
|
• compared to wild-type cells which cannot migrate to the wound area in a scratch-wound in vitro assay after 24 hours or only partial cover area when treated with TGFbeta, mutant cells cover the entire scratch area in absence of TGFbeta
|
|
|
• in culture, untreated cells exhibit ~3-fold greater proliferation compared to controls and Smad3 hepatocytes; after TGFbeta treatement, cells show reduced proliferation compared to controls
• in CCL4-injured livers, cell proliferation is higher at earlier time points than in controls or Smad3-deficient livers
|
Allelic
Composition |
Nodaltm1Rob/Nodal+
Smad2tm1.1Epb/Smad2+
|
|
Genetic
Background |
involves: 129S/SvEv * 129X1/SvJ * C57BL/6J * SJL |
|
|
|
nervous system
|
|
• in 1 of 41 mice between E10.5 and E12.5
|
embryo
|
|
• 15 of 41 mice exhibit anterior truncations or a severe growth delay
|
growth/size/body
|
|
• in 1 of 41 mice between E10.5 and E12.5
|
|
|
• 15 of 41 mice exhibit anterior truncations or a severe growth delay
|
respiratory system
taste/olfaction
vision/eye
|
|
• partial failure to separate eyes in 1 of 41 mice between E10.5 and E12.5
|
craniofacial
|
|
• in 1 of 41 mice between E10.5 and E12.5
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smad2tm1.1Epb mutation
(1 available);
any
Smad2 mutation
(50 available)
Smad3tm1Cxd mutation
(0 available);
any
Smad3 mutation
(18 available)
|
|
|
mortality/aging
|
|
• mice die between 1 and 8 months of age, due to primary defect in mucosal immune function
|
cellular
|
|
• after attachment to culture dishes, hepatocytes show relatively normal epithelial morphology but show wider cell-cell contacts and intracellular space compared to controls
|
|
|
• after treatment with TGFbeta, cells show little or no apoptosis, compared to control or Smad2 conditional knockout cells
|
Analysis Tools