Phenotypes Associated with This Genotype

Genotype
MGI:3758892

• Allelic Composition: Smad2^tm1Cxd/Smad2⁺; Smad3^tm1Cxd/Smad3⁺
• Genetic Background: involves: 129S6/SvEvTac * NIH Black Swiss

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:106308 )

• lethality by E14.5 due to hepatic dysplasia

embryonic lethality during organogenesis, incomplete penetrance ( J:70388 )

• 10 of 21 E8.5-E10.5 mutants suffer lethality due to patterning defects

growth/size/body

embryonic growth retardation ( J:106308 )

• severely affected mutants are growth retarded at E9.5

increased fetal size ( J:70388 )

• E14.5 mutants are somewhat larger in size

liver/biliary system

abnormal hepatoblast migration ( J:106308 )

• marker analysis indicates defects in hepatoblast migration

abnormal liver morphology ( J:70388 )

• liver architecture is distorted

• cultured livers from E10.5 mutants do not exhibit outgrowth of liver lobules with primitive bile ducts as in wild-type, instead, they suffer extensive cell death or fail to develop normal liver architecture

dilated liver sinusoidal space ( J:70388 )

• dilated sinusoidal spaces

delayed hepatic development ( J:106308 )

• marker analysis indicates a delay in hepatogenesis

abnormal hepatic cord morphology ( J:70388 )

• arrangement of hepatocytes is abnormal in E14.5 livers; hepatocytes are found in small clusters and cell plates are absent unlike in wild-type where cords of hepatocytes are distributed throughout in the parenchyma

small liver ( J:70388 )

• small livers but have the correct number of lobes and appear red

liver hypoplasia ( J:70388 , J:106308 )

• 100% of E14.5 mutants exhibit severe liver hypoplasia (J:70388)

• liver is reduced in some mutants at E12.5-E14.5 (J:106308)

abnormal hepatocyte physiology ( J:70388 )

• hepatocytes cultured in vitro fail to adhere well to various substrates, expression of beta1 integrin is lost, and E-cadherin is mislocalized, indicating that hepatocytes have abnormal adhesive properties

decreased hepatocyte proliferation ( J:70388 )

• liver cells are in a less proliferative state than in wild-type as indicated by PCNA antibody staining

hematopoietic system

increased erythrocyte cell number ( J:70388 )

• increase in the number of erythrocytes in E14.5 livers

craniofacial

abnormal craniofacial morphology ( J:70388 , J:106308 )

• 20% of E14.5 mutants exhibit craniofacial defects in addition to the liver hypoplaisa (J:70388)

• some embryos display craniofacial defects as early as E8.5 (J:106308)

cardiovascular system

dilated liver sinusoidal space ( J:70388 )

• dilated sinusoidal spaces

abnormal heart looping ( J:106308 )

• some embryos exhibit abnormal heart looping

abnormal pericardial cavity morphology ( J:106308 )

• some embryos exhibit an enlarged pericardiac cavity

digestive/alimentary system

abnormal foregut morphology ( J:106308 )

• anterior ventral foregut defects at E8.5 as indicated by marker analysis, showing that the definitive endoderm fails to displace the visceral endoderm at the anterior intestinal portal

embryo

abnormal developmental patterning ( J:106308 )

• 54 of 106 mutants display patterning abnormalities of varying severity at E9.5-E10.5

• some embryos display midline defects as early as E8.5

abnormal gastrulation ( J:106308 )

• gastrulation defects

abnormal endoderm development ( J:106308 )

• definitive endoderm is reduced at E8.5 as indicated by marker analysis

• mutants display defects in the specification of hepatogenic endoderm

embryonic growth retardation ( J:106308 )

• severely affected mutants are growth retarded at E9.5

abnormal somite development ( J:106308 )

• severely affected mutants exhibit irregular somites at E9.5

endocrine/exocrine glands

small thyroid gland ( J:106308 )

• reduced thyroid at E10.5

nervous system

holoprosencephaly ( J:106308 )

• seen in some mutants

vision/eye

cyclopia ( J:106308 )

• seen in some mutants

cellular

abnormal hepatoblast migration ( J:106308 )

• marker analysis indicates defects in hepatoblast migration

decreased hepatocyte proliferation ( J:70388 )

• liver cells are in a less proliferative state than in wild-type as indicated by PCNA antibody staining