Phenotypes Associated with This Genotype

Genotype
MGI:2182722

• Allelic Composition: Smad4^tm1Cxd/Smad4^tm1Cxd
• Genetic Background: involves: 129S6/SvEvTac

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

Morphological and molecular analyses of Smad4^tm1Cxd/Smad4^tm1Cxd embryos

mortality/aging

embryonic lethality between implantation and somite formation, incomplete penetrance ( J:46852 )

• most homozygotes die between E6.5 and E8.5

embryonic lethality between somite formation and embryo turning, incomplete penetrance ( J:46852 )

• at E8.5-E9.5, a small portion of homozygotes are still viable and exhibit an increased size relative to E6.5-E7.5 mutants

• at E8.5, some abnormal embryos resemble small solid balls while others show abnormally enlarged sac-like structures with presumptive embryonic endoderm and ectoderm

embryo

decreased inner cell mass proliferation ( J:46852 )

• after 5 days in culture, the ICM outgrowths of mutant embryos are only ~25%-50% the size of wild-type embryos

abnormal endoderm development ( J:46852 )

• in contrast to wild-type, none of the mutant ICM outgrowths display any signs of endoderm differentiation after 7 days in culture

embryonic growth arrest ( J:46852 )

• homozygotes are developmentally arrested at the onset of gastrulation, although some are still alive beyond E6.5

• little elongation in the extraembryonic portion of the late egg cylinder is observed

decreased embryo size ( J:46852 )

• at E6.5, homozygotes are only 25%-50% the size of wild-type or heterozygous embryos

• homozygotes remain significantly smaller than wild-type embryos at E7.5

abnormal embryonic tissue morphology ( J:46852 )

decreased embryonic epiblast cell proliferation ( J:46852 )

• at E6.5, homozygotes display reduced epiblast proliferation relative to wild-type embryos

absent egg cylinders ( J:46852 )

• at E6.5 and E7.5, homozygotes display either absent or significantly reduced and distorted extraembryonic egg cylinders; at E7.5, both types of abnormal embryos show larger embryonic portions than mutants at E6.5

absent mesoderm ( J:46852 )

• although a portion of mutant embryos at E8.5 display an increase in embryonic ectoderm and endoderm, they fail to form mesoderm

failure of primitive streak formation ( J:46852 )

• at E7.5, homozygotes lack an identifiable primitive streak and headfold

abnormal embryonic-extraembryonic boundary morphology ( J:46852 )

• at E6.5, homozygotes display no obvious boundary between the embryonic and extraembryonic portions

abnormal extraembryonic tissue morphology ( J:46852 )

• at E7.5, homozygotes exhibit a significantly reduced extraembryonic portion relative to E6.5 and E7.5 wild-type embryos

small ectoplacental cone ( J:46852 )

increased Reichert's membrane thickness ( J:46852 )

• at E7.5, homozygotes remain small but display a relatively large Reichert's membrane

growth/size/body

decreased embryo size ( J:46852 )

• at E6.5, homozygotes are only 25%-50% the size of wild-type or heterozygous embryos

• homozygotes remain significantly smaller than wild-type embryos at E7.5

cellular

decreased cell proliferation ( J:46852 )

• at E6.5, homozygotes exhibit significantly reduced epiblast cell proliferation, as shown by weak PCNA staining

decreased inner cell mass proliferation ( J:46852 )

• after 5 days in culture, the ICM outgrowths of mutant embryos are only ~25%-50% the size of wild-type embryos

decreased embryonic epiblast cell proliferation ( J:46852 )

• at E6.5, homozygotes display reduced epiblast proliferation relative to wild-type embryos