Phenotypes associated with this allele

• Allele Symbol: Ndst1^tm1Je
• Allele Name: targeted mutation 1, Jeffrey D Esko
• Allele ID: MGI:3589211
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ndst1^tm1Je/Ndst1^tm1Je Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:4439272
cn2	Ndst1^tm1Je/Ndst1^tm1Je Slit3^tm1.1Dor/Slit3^+ Tg(Tek-cre)1Ywa/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5562648
cn3	Ndst1^tm1Je/Ndst1^tm1Je Tg(Tek-cre)1Ywa/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3589869
cn4	Ndst1^tm1Je/Ndst1^tm1Je Robo4^tm1Kzh/Robo4^+ Tg(Tek-cre)1Ywa/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5562651
cn5	Ndst1^tm1Je/Ndst1^tm1Je Robo4^tm1Kzh/Robo4^tm1Kzh Tg(Tek-cre)1Ywa/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5562654
cn6	Ndst1^tm1Je/Ndst1^tm1Je Slit3^tm1.1Dor/Slit3^tm1.1Dor Tg(Tek-cre)1Ywa/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5562649
cn7	Ndst1^tm1Je/Ndst1^tm1Je Ndst2^tm1Lkj/Ndst2^tm1Lkj Tg(Tek-cre)1Ywa/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3589870

Genotype
MGI:4439272

cn1

• Allelic Composition: Ndst1^tm1Je/Ndst1^tm1Je; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

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

liver/biliary system

abnormal hepatocyte physiology ( J:158299 )

• hepatocytes exhibit decreased VLDL binding, uptake, and degradation compared with wild-type cells

Genotype
MGI:5562648

cn2

• Allelic Composition: Ndst1^tm1Je/Ndst1^tm1Je; Slit3^tm1.1Dor/Slit3⁺; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

muscle

diaphragmatic hernia ( J:208012 )

• mice develop central tendon congenital diaphragmatic hernia with the same penetrance as seen in single Ndst1 conditional homozygotes

Genotype
MGI:3589869

cn3

• Allelic Composition: Ndst1^tm1Je/Ndst1^tm1Je; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

immune system

abnormal leukocyte migration ( J:100456 )

• 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%

abnormal leukocyte adhesion ( J:100456 )

• a reduction of about 40% in firm adhesion of neutrophils to mutant endothelial cells is seen

impaired leukocyte tethering or rolling ( J:100456 )

• rolling velocity is about 40% greater on mutant endothelial cells at 1 dyne/cm² of shear force

decreased inflammatory response ( J:100456 )

• 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

abnormal leukocyte migration ( J:100456 )

• 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%

abnormal leukocyte adhesion ( J:100456 )

• a reduction of about 40% in firm adhesion of neutrophils to mutant endothelial cells is seen

impaired leukocyte tethering or rolling ( J:100456 )

• rolling velocity is about 40% greater on mutant endothelial cells at 1 dyne/cm² of shear force

decreased endothelial cell proliferation ( J:208012 )

• endothelial cell proliferation is reduced in central tendon

• however, mural cell recruitment is normal

hematopoietic system

abnormal leukocyte migration ( J:100456 )

• 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%

abnormal leukocyte adhesion ( J:100456 )

• a reduction of about 40% in firm adhesion of neutrophils to mutant endothelial cells is seen

impaired leukocyte tethering or rolling ( J:100456 )

• rolling velocity is about 40% greater on mutant endothelial cells at 1 dyne/cm² of shear force

cardiovascular system

abnormal vascular development ( J:208012 )

• 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

decreased angiogenesis ( J:208012 )

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

embryo

abnormal septum transversum morphology ( J:208012 )

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

homeostasis/metabolism

hypoxia ( J:208012 )

• increase in hypoxia in diaphragm

liver/biliary system

herniated liver ( J:208012 )

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

muscle

abnormal diaphragm morphology ( J:208012 )

• 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

abnormal diaphragm central tendon morphology ( J:208012 )

• 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

diaphragmatic hernia ( J:208012 )

• 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

thin diaphragm muscle ( J:208012 )

• muscular region of the diaphragm is thinner at E15.5

• however, fasciculi in the muscle are organized and sarcomeres appear normal

abnormal tendon cell morphology ( J:208012 )

• cell proliferation of tenocytes in the diaphragm is reduced

abnormal tendon collagen fibril morphology ( J:208012 )

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

skeleton

abnormal diaphragm central tendon morphology ( J:208012 )

• 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

abnormal tendon cell morphology ( J:208012 )

• cell proliferation of tenocytes in the diaphragm is reduced

abnormal tendon collagen fibril morphology ( J:208012 )

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

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

Genotype
MGI:5562651

cn4

• Allelic Composition: Ndst1^tm1Je/Ndst1^tm1Je; Robo4^tm1Kzh/Robo4⁺; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

cardiovascular system

abnormal vascular development ( J:208012 )

• 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

muscle

abnormal diaphragm morphology ( J:208012 )

• 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

diaphragmatic hernia ( J:208012 )

• 88% of mice develop congenital diaphragmatic hernia

Genotype
MGI:5562654

cn5

• Allelic Composition: Ndst1^tm1Je/Ndst1^tm1Je; Robo4^tm1Kzh/Robo4^tm1Kzh; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

cardiovascular system

abnormal vascular development ( J:208012 )

• diaphragm shows a large avascular region in the anterior tendon and reduced total vessel length and branch point numbers

muscle

abnormal diaphragm morphology ( J:208012 )

• diaphragm shows a large avascular region in the anterior tendon and reduced total vessel length and branch point numbers

diaphragmatic hernia ( J:208012 )

• 92% of mice develop congenital diaphragmatic hernia

Genotype
MGI:5562649

cn6

• Allelic Composition: Ndst1^tm1Je/Ndst1^tm1Je; Slit3^tm1.1Dor/Slit3^tm1.1Dor; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

muscle

diaphragmatic hernia ( J:208012 )

• 100% of mice develop central tendon congenital diaphragmatic hernia compared to 57% of conditional Ndst1 homozygotes and 86% of Slit3 homozygotes

Genotype
MGI:3589870

cn7

• Allelic Composition: Ndst1^tm1Je/Ndst1^tm1Je; Ndst2^tm1Lkj/Ndst2^tm1Lkj; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

mortality/aging

prenatal lethality, complete penetrance ( J:100456 )

• no pups carrying the cre transgene are born