Phenotypes Associated with This Genotype

Genotype
MGI:2178957

• Allelic Composition: Hspg2^tm1Ref/Hspg2^tm1Ref
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

Hemopericardium development in E10.5 Hspg2^tm1Ref/Hspg2^tm1Ref embryos

mortality/aging

perinatal lethality, incomplete penetrance ( J:58700 )

• 20-30% die perinatally with severe brain and skeletal defects

embryonic lethality during organogenesis, incomplete penetrance ( J:58700 )

• 70-80% die between E10.5 and E12.5 with heart defects

growth/size/body

short nasal bone ( J:58700 )

• shorter nasal bone

cleft palate ( J:58700 )

decreased embryo size ( J:84739 )

abnormal chest morphology ( J:84739 )

• thorax is narrowed

decreased body length ( J:84739 )

• trunk is shortened

disproportionate dwarf ( J:58700 , J:84739 )

embryo

decreased embryo size ( J:84739 )

limbs/digits/tail

short limbs ( J:58700 )

skeleton

abnormal skeleton morphology ( J:58700 )

• homozygotes that survive past the E10.5-E12.5 stage develop the following skeletal abnormalities:

abnormal cranium morphology ( J:58700 )

absent frontal bone ( J:58700 )

• absent in embryos with exencephaly

abnormal occipital bone morphology ( J:58700 )

• the occipital bone is shortened and undermineralized

absent parietal bone ( J:58700 )

• absent in embryos with exencephaly

abnormal sphenoid bone morphology ( J:58700 )

• the sphenoidal bone is shortened and undermineralized

absent neurocranium ( J:58700 )

• absent in embryos with exencephaly

abnormal ethmoid bone morphology ( J:58700 )

• the ethmoidal bone is shortened and undermineralized

short mandible ( J:58700 )

short nasal bone ( J:58700 )

• shorter nasal bone

domed cranium ( J:58700 )

• homozygotes without exencephaly have a domed skull

abnormal long bone morphology ( J:58700 , J:84739 )

• bony trabecula are oriented transversely to the long axis (J:58700)

abnormal long bone metaphysis morphology ( J:84739 )

• greatly shortened

decreased length of long bones ( J:58700 )

• long bones are about half the size of wild-type and have a bended shape

abnormal rib morphology ( J:84739 )

• size and shape of ribs are abnormal

abnormal spine curvature ( J:58700 )

• abnormally bent vertebral column

enlarged vertebral body ( J:84739 )

• vertebral bodies are increased in size and have an abnormal shape

abnormal bone marrow cavity morphology ( J:58700 )

• bones have small marrow cavities

increased compact bone thickness ( J:58700 )

• cortical bone is thickened

abnormal cartilage morphology ( J:58700 )

abnormal long bone epiphyseal plate morphology ( J:58700 , J:84739 )

• 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)

abnormal long bone hypertrophic chondrocyte zone ( J:58700 , J:84739 )

• hypertrophic chondrocytes have an atypical morphology (J:58700)

disorganized long bone epiphyseal plate ( J:58700 )

• disorganized growth plates characterized by absence of the typical columnar arrangement of hypertrophic chondrocytes

abnormal cartilage development ( J:84739 )

• 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

abnormal intervertebral disk development ( J:84739 )

• annulus does not form, however the nucleus pulposus does, but is located at the periphery of the disk

abnormal chondrocyte morphology ( J:58700 )

• hypertrophic chondrocytes have an increased density of organelles and distended cisternae of ER and the cytosol is enriched with free ribosomes and polysomes

chondrodystrophy ( J:58700 , J:84739 )

• develops between E15 and time of birth (J:58700)

decreased bone mineralization ( J:58700 )

• bones of the chondrocranium are undermineralized

• minimal or no mineral deposits in the matrix around hypertrophic chondroctyes

abnormal endochondral bone ossification ( J:84739 )

• all bones formed by endochondral bone ossification are malformed

nervous system

intracranial hemorrhage ( J:58700 )

abnormal nervous system morphology ( J:58700 )

• homozygotes that survive past the E10.5-E12.5 stage develop the following brain defects:

abnormal brain morphology ( J:58700 )

• 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

abnormal telencephalon morphology ( J:58700 )

• exhibit neuronal ectopias in the ventral telencephalic region

exencephaly ( J:58700 )

• seen in about 80% of embryos that survive to birth

cardiovascular system

abnormal ascending aorta and coronary artery attachment ( J:107987 )

• 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

dilated liver sinusoidal space ( J:80720 )

• sometimes the hepatic sinusoids are abnormally enlarged

abnormal cardinal vein morphology ( J:80720 )

• sometimes the posterior cardinal veins are abnormally enlarged

abnormal myocardium layer morphology ( J:80720 )

• exhibit signs of myocardial damage, including ruptures in the proximal conus and conoventricular junction

abnormal myocardium compact layer morphology ( J:58700 )

• 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

abnormal cardiac outflow tract development ( J:80720 )

• 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

absent conotruncal ridges ( J:80720 )

• 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

conotruncal ridge hyperplasia ( J:80720 )

• hyperplastic conotruncal endocardial cushions

abnormal conotruncus septation ( J:80720 )

• exhibit anomalous conotruncal septation

abnormal heart and great artery attachment ( J:107987 )

• aortic and pulmonary roots are arranged side by side, with the aortic root usually located at a slightly more ventral level

transposition of great arteries ( J:80720 , J:107987 )

• 73% of embryos surviving to E17.5 exhibit complete transposition of great arteries (TGA) (J:80720)

abnormal semilunar valve morphology ( J:80720 )

• 3 of 11 embryos with TGA show malformations of semilunar valves

abnormal aortic valve morphology ( J:80720 )

• asymmetrical and abnormal shapes of cushions which sometimes obstruct the vascular lumen

abnormal pulmonary valve morphology ( J:80720 )

• asymmetrical and abnormal shapes of cushions which sometimes obstruct the vascular lumen

abnormal pericardium morphology ( J:58700 )

• pericardial tissue is thickened because of an increase in cell number and matrix deposition

aneurysm ( J:58700 )

• between E13-E17, form microaneurysms associated with bleedings in several tissues

hemorrhage ( J:58700 )

• in several tissues including lung, skin, and brain

hemopericardium ( J:58700 )

• in mice the die around E10.5-E12.5

lung hemorrhage ( J:58700 )

intracranial hemorrhage ( J:58700 )

skin hemorrhage ( J:58700 )

irregular heartbeat ( J:58700 )

• weak heartbeat in mice that die between E10.5 and E12.5

hearing/vestibular/ear

abnormal inner ear morphology ( J:58700 )

• structures of the inner ear are poorly developed

abnormal middle ear morphology ( J:58700 )

• structures of the middle ear are poorly developed

craniofacial

abnormal cranium morphology ( J:58700 )

absent frontal bone ( J:58700 )

• absent in embryos with exencephaly

abnormal occipital bone morphology ( J:58700 )

• the occipital bone is shortened and undermineralized

absent parietal bone ( J:58700 )

• absent in embryos with exencephaly

abnormal sphenoid bone morphology ( J:58700 )

• the sphenoidal bone is shortened and undermineralized

absent neurocranium ( J:58700 )

• absent in embryos with exencephaly

abnormal ethmoid bone morphology ( J:58700 )

• the ethmoidal bone is shortened and undermineralized

short mandible ( J:58700 )

short nasal bone ( J:58700 )

• shorter nasal bone

domed cranium ( J:58700 )

• homozygotes without exencephaly have a domed skull

cleft palate ( J:58700 )

liver/biliary system

dilated liver sinusoidal space ( J:80720 )

• sometimes the hepatic sinusoids are abnormally enlarged

digestive/alimentary system

cleft palate ( J:58700 )

homeostasis/metabolism

hemopericardium ( J:58700 )

• in mice the die around E10.5-E12.5

integument

skin hemorrhage ( J:58700 )

respiratory system

lung hemorrhage ( J:58700 )

short nasal bone ( J:58700 )

• shorter nasal bone

cellular

impaired basement membrane formation ( J:58700 )

• 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

abnormal myocardium layer morphology ( J:80720 )

• exhibit signs of myocardial damage, including ruptures in the proximal conus and conoventricular junction

abnormal myocardium compact layer morphology ( J:58700 )

• 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