Mouse Genome Informatics
hm
    Hspg2tm1Ref/Hspg2tm1Ref
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Hemopericardium development in E10.5 Hspg2tm1Ref/Hspg2tm1Ref embryos

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
• thorax is narrowed
• trunk is shortened

embryogenesis

limbs/digits/tail

skeleton
• homozygotes that survive past the E10.5-E12.5 stage develop the following skeletal abnormalities:
• bones of the chondrocranium (occipital, sphenoidal, and ethmoidal) are shortened and undermineralized
• absent in embryos with exencephaly
• absent in embryos with exencephaly
• absent in embryos with exencephaly
• shorter nasal bone
• homozygotes without exencephaly have a domed skull
• bony trabecula are oriented transversely to the long axis (J:58700)
• 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)
• all bones formed by endochondral bone ossification are malformed
• bones of the chondrocranium are undermineralized
• minimal or no mineral deposits in the matrix around hypertrophic chondroctyes

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
• seen in about 80% of embryos that survive to birth
• exhibit neuronal ectopias in the ventral telencephalic region

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 anomalous conotruncal septation
• 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
• 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)
• 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
• 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
• 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
• bones of the chondrocranium (occipital, sphenoidal, and ethmoidal) are shortened and undermineralized
• absent in embryos with exencephaly
• absent in embryos with exencephaly
• absent in embryos with exencephaly
• shorter nasal bone
• homozygotes without exencephaly have a domed skull

liver/biliary system
• sometimes the hepatic sinusoids are abnormally enlarged

digestive/alimentary system

homeostasis/metabolism
• in mice the die around E10.5-E12.5

integument

respiratory system

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

Mouse Models of Human Disease
OMIM IDRef(s)
Dyssegmental Dysplasia, Silverman-Handmaker Type; DDSH 224410 J:84739
Transposition of the Great Arteries, Dextro-Looped 1; DTGA1 608808 J:80720 , J:107987