renal/urinary system
• urinary Na+ excretion was enhanced
|
• urinary DPD (degradation products of collagen I) concentration in homozygous mutant mice is reduced
|
limbs/digits/tail
long femur
(
J:217458
)
• small, albeit significant, increase in femur length
|
mortality/aging
• by E12.5, 52% of mutant embryos are dead with extensive bleeding; the remaining embryos survive to adulthood and appear grossly normal
|
neoplasm
N |
• when injected with B16-F10 melanoma cells via tail vein, homozygotes show no differences in hematogenous metastasis (tumor count or burden) relative to wild-type mice, indicating no protection against metastasis in this model
|
skeleton
N |
• osteoblast number and surface are not significantly different between controls and mutant mice
• no changes in osteoclast number and surface
|
long femur
(
J:217458
)
• small, albeit significant, increase in femur length
|
• diaphyseal endocortical volume is increased
• endocortical and cortical volumes are significantly increased
|
• trabecular bone volume fraction in the distal metaphyseal bone compartment is elevated
• significantly increased trabecular bone volume in the femoral metaphysis and diaphysis
|
• diaphyseal thickness was reduced
|
• trabecular separation is decreased
|
cardiovascular system
• at E8.75 to E10.5, embryos with gross bleeding are pale and display a disorganized yolk sac vasculature or delayed remodeling
|
• at E12.5, mutant yolk sacs lack blood-filled vessels
|
• at E9.5, 2 out of 3 mutant embryos exhibit a defect in the wall of the sinus venosus that is large enough to allow blood cells into the pericardial cavity
|
• at E9.5, hemorrhagic embryos often display a dilated pericardial sac, indicating cardiovascular failure
• at this stage, 4 out of 19 mutant embryos with microscopic bleeding display normal pericardial sacs
|
hemorrhage
(
J:71309
)
• by E9.5, ~66% of mutant embryos display microscopic bleeding in the pericardial and/or peritoneal, amniotic, and/or exocoelomic cavity
• live E9.5 to E10.5 embryos with both gross bleeding and vigorous heart beats are occasionally observed
|
• at E9.5, 22% of mutant embryos exhibit hemorrhage in the exocoelomic and/or pericardial cavities
|
cellular
• relative to wild-type, mutant endothelial cells display a 20-30% reduction in F10 (coagulation protease factor Xa)-triggered phosphoinositide hydrolysis
• a similar reduction is observed when ERK1/2 phosphorylation is used to assess F10 signaling
• in contrast, mutant lung fibroblasts exhibit a complete absence of F10-induced phosphoinositide hydrolysis
|
• cortical neurons from mutant fetuses exhibit a complete loss of activated protein C (APC)-mediated neuronal protection against NMDA-induced apoptosis
|
embryo
• at E8.75 to E10.5, embryos with gross bleeding are pale and display a disorganized yolk sac vasculature or delayed remodeling
|
• at E12.5, mutant yolk sacs lack blood-filled vessels
|
• at E9.5, mutant embryos show a variable developmental delay but no gross vascular anomalies
|
growth/size/body
• at E9.5, mutant embryos show a variable developmental delay but no gross vascular anomalies
|
nervous system
• cortical neurons from mutant fetuses exhibit a complete loss of activated protein C (APC)-mediated neuronal protection against NMDA-induced apoptosis
|
homeostasis/metabolism
N |
• urinary Ca2+ excretion is not affected
• serum Ca2+ concentration is not affected
• serum Na+ and K+ values appear similar to controls
|
• at E9.5, 22% of mutant embryos exhibit hemorrhage in the exocoelomic and/or pericardial cavities
|
• serum RANKL level is significantly decreased, and the OPG level is increased, resulting in a significantly reduced RANKL/OPG ratio
|
• urinary Na+ excretion was enhanced
|
• serum RANKL level is significantly decreased
|
• serum osteoprotegerin (OPG) level is increased
|
• urinary DPD (degradation products of collagen I) concentration in homozygous mutant mice is reduced
|