Mouse Genome Informatics
ht
    Gt(ROSA)26Sortm3(tetO-EGFP,-RNAi:T)Bgh/Gt(ROSA)26Sor
involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NCr * NMRI
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• mice from pregnant females treated with doxycycline that survive to birth die within a few hours after birth due to respiratory distress
• embryos from pregnant females treated with doxycycline exhibit increased mortality after E12.5, with only 35% surviving past E13.5

embryogenesis
• caudal somites are absent at E12.5 in embryos from pregnant females treated with doxycycline but they are present at E10.5, indicating loss of mesodermal tissue between E10.5 and E12.5
• embryos from pregnant females treated with doxycycline exhibit unstructured mesodermal tissue posterior to the hindlimb bud by E12.5
• severe reduction in paraxial mesenchyme in the area surrounding the notochord, located between the cloaca and neural tube, in E10.5 embryos from pregnant females treated with doxycycline
• E12.5 embryos from pregnant females treated with doxycycline exhibit increased cell death in caudal mesenchyme
• embryos from pregnant females treated with doxycycline develop severe caudal defects posterior to the hindlimb by E12.5 and exhibit caudal regression
• embryos from pregnant females treated with doxycycline exhibit a wide but covered opening it the caudal neural tube by E12.5-E13.5
• mice from pregnant females treated with doxycycline that survive to birth exhibit spina bifida occulta
• embryos from pregnant females treated with doxycycline exhibit a kinked neural tube located at the level between the fore and hindlimb buds at E10.5
• notochord structure is undifferentiated in E10.5 embryos from pregnant females treated with doxycycline, appearing larger and more tubular in structure rather than the compact morphology seen in controls and marker analysis indicates it adopts a neural character
• no detectable notochord is seen at the level of the hindlimb in E12.5 embryos from pregnant females treated with doxycycline, indicating that the undifferentiated notochord seen at E12.5 degenerates by E12.5
• embryos from pregnant females treated with doxycycline exhibit notochord arrest near the forelimb level at E9.5-E10.5, however they have a normal number of somites at this stage
• disrupted somites are seen in E12.5 embryos from pregnant females treated with doxycycline
• caudal somites are absent at E12.5 in embryos from pregnant females treated with doxycycline but they are present at E10.5, indicating loss of mesodermal tissue/degeneration of somites between E10.5 and E12.5

nervous system
• embryos from pregnant females treated with doxycycline exhibit a wide but covered opening it the caudal neural tube by E12.5-E13.5
• mice from pregnant females treated with doxycycline that survive to birth exhibit spina bifida occulta
• embryos from pregnant females treated with doxycycline exhibit a kinked neural tube located at the level between the fore and hindlimb buds at E10.5

digestive/alimentary system
• mutants from pregnant females treated with doxycycline exhibit various anorectal defects
• seen in E13.5-P0 mutants from pregnant females treated with doxycycline
• seen in E13.5-P0 mutants from pregnant females treated with doxycycline
• seen in E13.5-P0 mutants from pregnant females treated with doxycycline

limbs/digits/tail
• embryos from pregnant females treated with doxycycline exhibit a rudimentary tail between E10.5 and E11.5
• mice from pregnant females treated with doxycycline that survive to birth exhibit a tail filament
• majority of E18.5 mutants from pregnant females treated with doxycycline have no caudal vertebrae and the remaining have only a few, malformed caudal vertebrae with an absence of sacral vertebrae
• 30% incidence of C7 to T1 homeotic transformation in E18.5 mutants from pregnant females treated with doxycycline

renal/urinary system
• mutants from pregnant females treated with doxycycline exhibit various anorectal defects
• seen in one mutant from a pregnant female treated with doxycycline
• seen in E13.5-P0 mutants from pregnant females treated with doxycycline

respiratory system
• surviving mutants from pregnant females treated with doxycycline exhibit respiratory distress at birth

skeleton
• in 6 of 9 mutants from pregnant females treated with doxycycline, the vertebral column is generally arrested at the lumbar/sacral level with several poorly developed lumbar vertebrae and a sacral rudiment at E18.5
• mice from pregnant females treated with doxycycline that survive to birth exhibit spina bifida occulta
• majority of E18.5 mutants from pregnant females treated with doxycycline have no caudal vertebrae and the remaining have only a few, malformed caudal vertebrae with an absence of sacral vertebrae
• 30% incidence of C7 to T1 homeotic transformation in E18.5 mutants from pregnant females treated with doxycycline
• mutants from pregnant females treated with doxycycline exhibit poorly developed lumbar vertebrae at E18.5
• mutants from pregnant females treated with doxycycline exhibit only a sacral rudiment or absence of sacral vertebrae at E18.5

Mouse Models of Human Disease
OMIM IDRef(s)
Sacral Defect with Anterior Meningocele 600145 J:190628