All Phenotypes Tbx4<tm1Pa> MGI Mouse

embryonic lethality during organogenesis, complete penetrance ( J:83256 )

• death by E10.5

abnormal umbilical artery morphology ( J:83256 )

• at E10.5, mutant embryos lack large umbilical blood vessels and exhibit a compact amorphous mass surrounding blood-filled vesicles

• no leakage of blood from the residual allantois into the yolk sac cavity is observed

increased allantois apoptosis ( J:83256 )

• at E10.5, the mutant allantois displays dense, irregularly packed cells with multiple double-walled vesicles and numerous pyknotic nuclei

• at E8.0, TUNEL assays indicate extensive apoptotic cell death over the entire distal tip of the mutant allantois; in constrast, cell proliferation is comparable to that of wild-type embryos

small hindlimb buds ( J:83256 )

• mutant hindlimb buds fail to develop and do not maintain Fgf10 expression in the mesenchyme, despite successful induction of the hindlimb bud, and of many outgrowth and patterning genes therein

• at the 30-32-somite stage mutant embryos exhibit smaller hindlimb buds relative to somite-matched wild-type embryos

• in culture, mutant hindlimb explants fail to develop any obvious limb structures, despite the presence of a morphologically detectable hindlimb bud

abnormal allantois morphology ( J:83256 )

small allantois ( J:83256 )

• by E9.5, the mutant allantois has formed only a small, amorphous stump

absent umbilical cord ( J:83256 )

• by E9.5, the allantois of wild-type embryos has formed a thick, vascular umbilicus connecting it to the placenta; in contrast, mutant embryos remain loose in the yolk sac

• absence of the umbilicus alters normal blood flow patterns

failure of chorioallantoic fusion ( J:83256 )

• at E8.0, homozygotes exhibit failure of chorioallantoic fusion, although 15% of mutant allantoises do extend into the dome of the chorion at the 4- to 5-somite stage

• at E10.5, less than 1% of homozygotes show allantoic attachment to the chorion at only a single site; however, the allantois is small and abnormal, consisting of multiple blood-filled chambers, and no continuous vessel between the embryo and the placenta is formed

delayed allantois development ( J:83256 )

• at E8.0, homozygotes exhibit a short, unfused allantois: at the 6- to 8-somite stage, nearly all wild-type and heterozygous embryos have undergone chorioallantoic fusion, whereas most mutant embryos are still at the early allantois stage

• in contrast to normal development, the mutant allantois exhibits no cavitation near the distal tip

abnormal umbilical artery morphology ( J:83256 )

• at E10.5, mutant embryos lack large umbilical blood vessels and exhibit a compact amorphous mass surrounding blood-filled vesicles

• no leakage of blood from the residual allantois into the yolk sac cavity is observed

abnormal vascular regression ( J:83256 )

• homozygotes exhibit a block in vascular remodeling in the allantois: mutant endothelial cells differentiate from allantoic mesenchyme but remain as discreet clumps of cells and fail to remodel into primary vessels

pericardial edema ( J:83256 )

• at 10.5 dpc, some mutant embryos display pericardial edema, apparently as a result of abnormal blood flow patterns

distended pericardium ( J:83256 )

• at E10.5, some mutant embryos show swollen pericardial sacs

hemorrhage ( J:83256 )

• by E10.5, some mutant embryos are hemorrhagic and exhibit only the stump of an allantois while others are dead