Analysis Tools
mortality/aging
|
• 20-30% die perinatally with severe brain and skeletal defects
|
|
• 70-80% die between E10.5 and E12.5 with heart defects
|
growth/size/body
|
• shorter nasal bone
|
cleft palate
(
J:58700
)
|
• thorax is narrowed
|
|
• trunk is shortened
|
embryo
limbs/digits/tail
short limbs
(
J:58700
)
skeleton
|
• homozygotes that survive past the E10.5-E12.5 stage develop the following skeletal abnormalities:
|
|
• absent in embryos with exencephaly
|
|
• the occipital bone is shortened and undermineralized
|
|
• absent in embryos with exencephaly
|
|
• the sphenoidal bone is shortened and undermineralized
|
|
• absent in embryos with exencephaly
|
|
• the ethmoidal bone is shortened and undermineralized
|
|
• shorter nasal bone
|
domed cranium
(
J:58700
)
|
• homozygotes without exencephaly have a domed skull
|
|
• bony trabecula are oriented transversely to the long axis
(J:58700)
|
|
• greatly shortened
|
|
• long bones are about half the size of wild-type and have a bended shape
|
|
• size and shape of ribs are abnormal
|
|
• abnormally bent vertebral column
|
|
• vertebral bodies are increased in size and have an abnormal shape
|
|
• bones have small marrow cavities
|
|
• cortical bone is thickened
|
|
• growth plates are dissociated from their epiphses
(J:58700)
• growth plate cartilage lacks a collagen network and has shorter collagen fibrils
(J:58700)
• epiphyseal cartilages are enlarged and frequently contain holes or cracks, especially in the hypertrophic and prehypertrophic zones
(J:84739)
|
|
• hypertrophic chondrocytes have an atypical morphology
(J:58700)
|
|
• disorganized growth plates characterized by absence of the typical columnar arrangement of hypertrophic chondrocytes
|
|
• in resting zone, collagen fibrillar density is reduced but the length and diameter of fibrils is normal
• in the proliferating zone and the hypertrophic zone, collagen fibrillar density is further reduced and fibrils are very short, vary in diameter, and do not form a network
|
|
• annulus does not form, however the nucleus pulposus does, but is located at the periphery of the disk
|
|
• hypertrophic chondrocytes have an increased density of organelles and distended cisternae of ER and the cytosol is enriched with free ribosomes and polysomes
|
|
• develops between E15 and time of birth
(J:58700)
|
|
• bones of the chondrocranium are undermineralized
• minimal or no mineral deposits in the matrix around hypertrophic chondroctyes
|
|
• all bones formed by endochondral bone ossification are malformed
|
nervous system
|
• homozygotes that survive past the E10.5-E12.5 stage develop the following brain defects:
|
|
• some mice have holes in the forebrain and midbrain and show collapsed brain vesicles
• surface ectoderm of the cephalic regions has small clefts that contain round cells with small extensions
• brain tissue invades into the cephalic mesenchyme and fuses with the overlaying ectoderm
|
|
• exhibit neuronal ectopias in the ventral telencephalic region
|
exencephaly
(
J:58700
)
|
• seen in about 80% of embryos that survive to birth
|
cardiovascular system
|
• embryos with complete transposition of arteries, show a coronary artery pattern consisting of right and left coronary arteries arising from the dorsal and ventral sinuses of Valsalva, respectively
|
|
• sometimes the hepatic sinusoids are abnormally enlarged
|
|
• sometimes the posterior cardinal veins are abnormally enlarged
|
|
• exhibit signs of myocardial damage, including ruptures in the proximal conus and conoventricular junction
|
|
• the compact layer of cardiomyocytes is interrupted by small intercellular clefts and in a few embryos, the clefts in the myocardium are filled with endocardial cells
|
|
• mesenchymal cells in cardiac jelly of the outflow tract are abnormally abundant by E9.5
• at E10.5, lack defined endocardial ridges and have anomalous excess of mesenchymal cells in the outflow tract, resulting in a rounded or irregular conus lumen
|
|
• most of the mesenchyme in the proximal conus is irregularly dispersed throughout the extracellular matrix and defined endocardial ridges are not recognizable
• at E10.5, lack defined endocardial ridges and have anomalous excess of mesenchymal cells in the outflow tract, resulting in a rounded or irregular conus lumen
|
|
• hyperplastic conotruncal endocardial cushions
|
|
• exhibit anomalous conotruncal septation
|
|
• aortic and pulmonary roots are arranged side by side, with the aortic root usually located at a slightly more ventral level
|
|
• 73% of embryos surviving to E17.5 exhibit complete transposition of great arteries (TGA)
(J:80720)
|
|
• 3 of 11 embryos with TGA show malformations of semilunar valves
|
|
• asymmetrical and abnormal shapes of cushions which sometimes obstruct the vascular lumen
|
|
• asymmetrical and abnormal shapes of cushions which sometimes obstruct the vascular lumen
|
|
• pericardial tissue is thickened because of an increase in cell number and matrix deposition
|
|
• between E13-E17, form microaneurysms associated with bleedings in several tissues
|
hemorrhage
(
J:58700
)
|
• in several tissues including lung, skin, and brain
|
|
• in mice the die around E10.5-E12.5
|
|
• weak heartbeat in mice that die between E10.5 and E12.5
|
hearing/vestibular/ear
|
• structures of the inner ear are poorly developed
|
|
• structures of the middle ear are poorly developed
|
craniofacial
|
• absent in embryos with exencephaly
|
|
• the occipital bone is shortened and undermineralized
|
|
• absent in embryos with exencephaly
|
|
• the sphenoidal bone is shortened and undermineralized
|
|
• absent in embryos with exencephaly
|
|
• the ethmoidal bone is shortened and undermineralized
|
|
• shorter nasal bone
|
domed cranium
(
J:58700
)
|
• homozygotes without exencephaly have a domed skull
|
cleft palate
(
J:58700
)
liver/biliary system
|
• sometimes the hepatic sinusoids are abnormally enlarged
|
digestive/alimentary system
cleft palate
(
J:58700
)
homeostasis/metabolism
|
• in mice the die around E10.5-E12.5
|
integument
respiratory system
|
• shorter nasal bone
|
cellular
|
• cardiac muscle cells lack basement membrane or are covered by abnormal basement membrane
• basement membrane surrounding the telencephalic vesicles is disrupted in 70% of E11.5 embryos
|
muscle
|
• exhibit signs of myocardial damage, including ruptures in the proximal conus and conoventricular junction
|
|
• the compact layer of cardiomyocytes is interrupted by small intercellular clefts and in a few embryos, the clefts in the myocardium are filled with endocardial cells
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| dextro-looped transposition of the great arteries | DOID:0060770 |
OMIM:608808 |
J:80720 , J:107987 | |
| Silverman-Handmaker type dyssegmental dysplasia | DOID:0090032 |
OMIM:224410 |
J:84739 | |
