Analysis Tools
liver/biliary system
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• hepatocytes exhibit decreased VLDL binding, uptake, and degradation compared with wild-type cells
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Allele Symbol Allele Name Allele ID |
Ndst1tm1Je targeted mutation 1, Jeffrey D Esko MGI:3589211 |
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| Summary |
7 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• hepatocytes exhibit decreased VLDL binding, uptake, and degradation compared with wild-type cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop central tendon congenital diaphragmatic hernia with the same penetrance as seen in single Ndst1 conditional homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in an air-pouch model leukocyte infiltration is reduced to about half that of wild-type
• chemokine induced-immigration of neutrophils is reduced by about 50%
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• a reduction of about 40% in firm adhesion of neutrophils to mutant endothelial cells is seen
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• rolling velocity is about 40% greater on mutant endothelial cells at 1 dyne/cm2 of shear force
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• about 40% fewer neutrophils infiltrate the peritoneal cavity in response to intraperitoneal thioglycollate injection
• about 32% less ear thickening is seen in a model of contact dermatitis induced by oxazolone
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• in an air-pouch model leukocyte infiltration is reduced to about half that of wild-type
• chemokine induced-immigration of neutrophils is reduced by about 50%
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• a reduction of about 40% in firm adhesion of neutrophils to mutant endothelial cells is seen
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• rolling velocity is about 40% greater on mutant endothelial cells at 1 dyne/cm2 of shear force
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• endothelial cell proliferation is reduced in central tendon
• however, mural cell recruitment is normal
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• in an air-pouch model leukocyte infiltration is reduced to about half that of wild-type
• chemokine induced-immigration of neutrophils is reduced by about 50%
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• a reduction of about 40% in firm adhesion of neutrophils to mutant endothelial cells is seen
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• rolling velocity is about 40% greater on mutant endothelial cells at 1 dyne/cm2 of shear force
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• vascularization defects in the developing diaphragm
• central tendon of the diaphragm at E15.5 contains a larger avascular region than in controls and at E16.6, formation of the capillary bed in this region remains incomplete
• the central tendon shows reduced vessel density and many missing connections at E15.5 and E16.5
• the primary plexus of blood vessels in diaphragmatic muscle shows fewer vascular floors, reduced vascular density, some slender and cord-like capillaries, and capillary density remains reduced at E18.5
• however capillary density appears normal in the brain, liver, kidney, heart, lung, spleen and thymus
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• SLIT3-induced angiogenesis is greatly diminished in cornea micropocket experiments
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• adults show reduced branches of large vessels in the anterior muscular region of septum transversum
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• in most mice, liver is the only herniated organ although in a few cases, the small intestine is involved
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• diaphragm covering the liver is thinner at P1
• vascularization defects in the developing diaphragm
• the primary plexus of blood vessels in diaphragmatic muscle shows fewer vascular floors, reduced vascular density, some slender and cord-like capillaries, and capillary density remains reduced at E18.5
• increase in apoptosis in the diaphragm tendon
• cell proliferation of tenocytes in the diaphragm is reduced
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• the central tendon and liver remain fused at P1 unlike in wild-type where they are completely separated
• decrease in thickness and disorganized fibrils are seen in the primordial tendon at E15.5, indicating that genesis of the central tendon in the diaphragm is disrupted
• central tendon at E15.5 contains a larger avascular region than in controls and at E16.6, formation of the capillary bed in this region remains incomplete
• the central tendon shows reduced vessel density and many missing connections at E15.5 and E16.5
• mice show fewer tip endothelial cells (which guide angiogenic sprouting) in central tendon than in controls
• filopodia of tip cells are fewer in number and much shorter
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• 40% of mice develop congenital diaphragmatic hernia at P2, with penetrance increasing to 60% in adults
• hernia occurs at the anterior midline of the septum transversum in the diaphragm
• hernia size does not progress with age
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• muscular region of the diaphragm is thinner at E15.5
• however, fasciculi in the muscle are organized and sarcomeres appear normal
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• cell proliferation of tenocytes in the diaphragm is reduced
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• collagen bundle in the diaphragm is poorly expressed and disorganized, with fewer tenocytes
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• the central tendon and liver remain fused at P1 unlike in wild-type where they are completely separated
• decrease in thickness and disorganized fibrils are seen in the primordial tendon at E15.5, indicating that genesis of the central tendon in the diaphragm is disrupted
• central tendon at E15.5 contains a larger avascular region than in controls and at E16.6, formation of the capillary bed in this region remains incomplete
• the central tendon shows reduced vessel density and many missing connections at E15.5 and E16.5
• mice show fewer tip endothelial cells (which guide angiogenic sprouting) in central tendon than in controls
• filopodia of tip cells are fewer in number and much shorter
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• cell proliferation of tenocytes in the diaphragm is reduced
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• collagen bundle in the diaphragm is poorly expressed and disorganized, with fewer tenocytes
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| congenital diaphragmatic hernia | DOID:3827 |
OMIM:142340 OMIM:222400 OMIM:610187 |
J:208012 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice show delayed diaphragm vascularization and have more severe branching defects, including missing connections, lack of sprouting, and formation of coiled ends compared to single conditional Ndst1 homozygotes
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• mice show delayed diaphragm vascularization and have more severe branching defects, including missing connections, lack of sprouting, and formation of coiled ends compared to single conditional Ndst1 homozygotes
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• 88% of mice develop congenital diaphragmatic hernia
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• diaphragm shows a large avascular region in the anterior tendon and reduced total vessel length and branch point numbers
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• diaphragm shows a large avascular region in the anterior tendon and reduced total vessel length and branch point numbers
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• 92% of mice develop congenital diaphragmatic hernia
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 100% of mice develop central tendon congenital diaphragmatic hernia compared to 57% of conditional Ndst1 homozygotes and 86% of Slit3 homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• no pups carrying the cre transgene are born
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/23/2024 MGI 6.23 |
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