Phenotypes associated with this allele

• Allele Symbol: Smad2^tm1.1Epb
• Allele Name: targeted mutation 1.1, Erwin P Bottinger
• Allele ID: MGI:3703160
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Smad2^tm1.1Epb/Smad2^tm1.1Epb Smad3^tm1Cxd/Smad3^tm1Cxd Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * DBA * SJL	MGI:3703883
cn2	Smad2^tm1.1Epb/Smad2^tm1.1Epb Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129/Sv * C57BL/6 * DBA * SJL	MGI:3703880
cx3	Nodal^tm1Rob/Nodal^+ Smad2^tm1.1Epb/Smad2^+	involves: 129S/SvEv * 129X1/SvJ * C57BL/6J * SJL	MGI:5791937
cx4	Smad2^tm1.1Epb/Smad2^tm1.1Epb Smad3^tm1Cxd/Smad3^tm1Cxd	involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * SJL	MGI:3703878

Genotype
MGI:3703883

cn1

• Allelic Composition: Smad2^tm1.1Epb/Smad2^tm1.1Epb; Smad3^tm1Cxd/Smad3^tm1Cxd; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * DBA * SJL

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

liver/biliary system

liver/biliary system phenotype ( J:119642 )

N • mice exhibit normal postnatal liver and body growth and function

cellular

abnormal cell morphology ( J:119642 )

• only a few hepatocytes attach with atypical morphology after seeding

abnormal cell physiology ( J:119642 )

• isolated primary hepatocytes show decreased viability immediately upon isolation, prior to plating (<70% viable cells) compared to controls or other mutant genotypes

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:119642 )

• injection of CCL4 to the liver induces a greater degree of liver injury in mice compared to control or individual single knockout mice; advanced bridging central injury is induced in livers

Genotype
MGI:3703880

cn2

• Allelic Composition: Smad2^tm1.1Epb/Smad2^tm1.1Epb; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129/Sv * C57BL/6 * DBA * SJL

liver/biliary system

liver/biliary system phenotype ( J:119642 )

N • mice exhibit normal postnatal liver and body growth and function

abnormal hepatocyte morphology ( J:119642 )

• 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

abnormal hepatocyte physiology ( J:119642 )

• hepatocytes express much higher levels of vimentin (mesenchymal marker) compared to control or Smad3 mutant cells

increased hepatocyte proliferation ( J:119642 )

• 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

abnormal cell differentiation ( J:119642 )

• hepatocytes dedifferentiate spontaneously to acquire mesenchymal and promigratory features in culture

abnormal cell migration ( J:119642 )

• 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

increased hepatocyte proliferation ( J:119642 )

• 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

Genotype
MGI:5791937

cx3

• Allelic Composition: Nodal^tm1Rob/Nodal⁺; Smad2^tm1.1Epb/Smad2⁺
• Genetic Background: involves: 129S/SvEv * 129X1/SvJ * C57BL/6J * SJL

nervous system

holoprosencephaly ( J:183402 )

• in 1 of 41 mice between E10.5 and E12.5

embryo

embryonic growth retardation ( J:183402 )

• 15 of 41 mice exhibit anterior truncations or a severe growth delay

growth/size/body

abnormal olfactory epithelium morphology ( J:183402 )

• single field

proboscis ( J:183402 )

• in 1 of 41 mice between E10.5 and E12.5

embryonic growth retardation ( J:183402 )

• 15 of 41 mice exhibit anterior truncations or a severe growth delay

respiratory system

abnormal olfactory epithelium morphology ( J:183402 )

• single field

taste/olfaction

abnormal olfactory epithelium morphology ( J:183402 )

• single field

vision/eye

abnormal eye development ( J:183402 )

• partial failure to separate eyes in 1 of 41 mice between E10.5 and E12.5

craniofacial

abnormal olfactory epithelium morphology ( J:183402 )

• single field

proboscis ( J:183402 )

• in 1 of 41 mice between E10.5 and E12.5

Genotype
MGI:3703878

cx4

• Allelic Composition: Smad2^tm1.1Epb/Smad2^tm1.1Epb; Smad3^tm1Cxd/Smad3^tm1Cxd
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * SJL

mortality/aging

premature death ( J:119642 )

• mice die between 1 and 8 months of age, due to primary defect in mucosal immune function

cellular

abnormal cell morphology ( J:119642 )

• after attachment to culture dishes, hepatocytes show relatively normal epithelial morphology but show wider cell-cell contacts and intracellular space compared to controls

decreased apoptosis ( J:119642 )

• after treatment with TGFbeta, cells show little or no apoptosis, compared to control or Smad2 conditional knockout cells