Mouse Genome Informatics
cn
    Ndst1tm1Je/Ndst1tm1Je
Tg(Tek-cre)1Ywa/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
immune system
• 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%
• rolling velocity is about 40% greater on mutant endothelial cells at 1 dyne/cm2 of shear force
• a reduction of about 40% in firm adhesion of neutrophils to mutant endothelial cells is seen
• 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

cellular
• 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%
• rolling velocity is about 40% greater on mutant endothelial cells at 1 dyne/cm2 of shear force
• a reduction of about 40% in firm adhesion of neutrophils to mutant endothelial cells is seen
• endothelial cell proliferation is reduced in central tendon
• however, mural cell recruitment is normal

hematopoietic system
• 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%
• rolling velocity is about 40% greater on mutant endothelial cells at 1 dyne/cm2 of shear force
• a reduction of about 40% in firm adhesion of neutrophils to mutant endothelial cells is seen

cardiovascular system
• 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
• SLIT3-induced angiogenesis is greatly diminished in cornea micropocket experiments

embryogenesis
• adults show reduced branches of large vessels in the anterior muscular region of septum transversum

homeostasis/metabolism
• increase in hypoxia in diaphragm

liver/biliary system
• in most mice, liver is the only herniated organ although in a few cases, the small intestine is involved

muscle
• 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
• 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
• muscular region of the diaphragm is thinner at E15.5
• however, fasciculi in the muscle are organized and sarcomeres appear normal
• 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
• collagen bundle in the diaphragm is poorly expressed and disorganized, with fewer tenocytes

skeleton
• 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
• collagen bundle in the diaphragm is poorly expressed and disorganized, with fewer tenocytes

Mouse Models of Human Disease
OMIM IDRef(s)
Diaphragmatic Hernia, Congenital 142340 J:208012