Phenotypes associated with this allele

• Allele Symbol: Tbx4^tm1.1Pa
• Allele Name: targeted mutation 1.1, Virginia Papaioannou
• Allele ID: MGI:2663716
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tbx4^tm1.1Pa/Tbx4^tm1.1Pa	involves: 129S1/Sv * 129X1/SvJ	MGI:2663719
ht2	Tbx4^tm1.1Pa/Tbx4^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3609957
cn3	Tbx4^tm1.1Pa/Tbx4^tm1.2Pa Tg(Prrx1-cre)1Cjt/0	involves: 129 * C57BL/6J * FVB/N * SJL/J	MGI:3811612

Genotype
MGI:2663719

hm1

• Allelic Composition: Tbx4^tm1.1Pa/Tbx4^tm1.1Pa
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

mortality/aging

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

• homozygotes die by E10.5 due to failure of chorioallantoic fusion

embryo

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

cardiovascular system

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

limbs/digits/tail

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

homeostasis/metabolism

pericardial edema ( J:83256 )

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

cellular

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

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

Genotype
MGI:3609957

ht2

• Allelic Composition: Tbx4^tm1.1Pa/Tbx4⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

embryo

delayed chorioallantoic fusion ( J:83256 )

• at E8.0, heterozygotes exhibit a delay in chorioallantoic fusion; however, all heterozygous embryos undergo chorioallantoic fusion past the 8-somite stage and appear indistinguishable from wild-type embryos

delayed allantois development ( J:83256 )

• at the 4- to 5-somite stage, heterozygotes display a lag in allantois development relative to somite-matched wild-type embryos dissected at E8.0

Genotype
MGI:3811612

cn3

• Allelic Composition: Tbx4^tm1.1Pa/Tbx4^tm1.2Pa; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: 129 * C57BL/6J * FVB/N * SJL/J

limbs/digits/tail

fused phalanges ( J:117423 )

• at E15.5, mice exhibit mild or nonexistent anterior digit fusions

brachydactyly ( J:117423 )

• the second digit of the foot is reduced compared to in wild-type mice

fused tarsal bones ( J:117423 )

• mice exhibit a partial fusion of the tarsals

abnormal hindlimb morphology ( J:117423 )

• hindlimbs are turned nearly backwards and do not articulate with the pelvis unlike in wild-type mice

• however, despite reduced hindlimb features apoptosis rates in the hindlimb are normal

short femur ( J:117423 )

• at E15.5, mice exhibit severely hypoplastic femurs that fail to ossify

short fibula ( J:117423 )

• at E15.5, mice exhibit hypoplastic fibulas that fail to ossify

skeleton

fused phalanges ( J:117423 )

• at E15.5, mice exhibit mild or nonexistent anterior digit fusions

fused tarsal bones ( J:117423 )

• mice exhibit a partial fusion of the tarsals

short femur ( J:117423 )

• at E15.5, mice exhibit severely hypoplastic femurs that fail to ossify

short fibula ( J:117423 )

• at E15.5, mice exhibit hypoplastic fibulas that fail to ossify

abnormal pelvic girdle bone morphology ( J:117423 )

• at E15.5, mice exhibit hypoplastic pelvis

• the ischium is fused to the illeum

• neonates exhibit small hips

abnormal ischium morphology ( J:117423 )

• the pelvic rami are absent and the ischium is fused to the illeum

• however, apoptosis rates in the hindlimb are normal