Phenotypes associated with this allele

• Allele Symbol: Robo4^tm1Kzh
• Allele Name: targeted mutation 1, Kang Zhang
• Allele ID: MGI:3785556
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Robo4^tm1Kzh/Robo4^tm1Kzh	involves: C57BL/6	MGI:3796169
hm2	Robo4^tm1Kzh/Robo4^tm1Kzh	Not Specified	MGI:6458566
cn3	Ndst1^tm1Je/Ndst1^tm1Je Robo4^tm1Kzh/Robo4^+ Tg(Tek-cre)1Ywa/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5562651
cn4	Ndst1^tm1Je/Ndst1^tm1Je Robo4^tm1Kzh/Robo4^tm1Kzh Tg(Tek-cre)1Ywa/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5562654

Genotype
MGI:3796169

hm1

• Allelic Composition: Robo4^tm1Kzh/Robo4^tm1Kzh
• Genetic Background: involves: C57BL/6

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

cardiovascular system

abnormal vascular development ( J:208012 )

• E15.5 diaphragms show slightly disrupted vascular development in the diaphragm

abnormal angiogenesis ( J:133680 )

• in vitro tube formation by endothelial cells in response to VEGF fails to stop in response to SLIT2

decreased angiogenesis ( J:208012 )

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

abnormal vascular permeability ( J:133680 )

• retinal endothelium has a higher basal permability than wild-type mice

• mice are refractory to SLIT2 or SLIT3 prevention of vascular leakiness of the retina caused by VEGF administration into the vitreous of the eye

pathological neovascularization ( J:133680 )

• retinopathy caused by exposure to hypoxic followed by hyperoxic conditions is more severe in these mice with a third more neovascularization occuring

• this retinopathy is refactory to SLIT2 treatment

respiratory system

abnormal lung endothelial cell migration ( J:133680 )

• lung endothelial cells fail to stop migrating up a VEGF gradient in response to SLIT-2

cellular

abnormal lung endothelial cell migration ( J:133680 )

• lung endothelial cells fail to stop migrating up a VEGF gradient in response to SLIT-2

homeostasis/metabolism

impaired skin barrier function ( J:133680 )

• mice are refractory to SLIT2 prevention of endothelial leakiness caused by VEGF administration into the skin

integument

impaired skin barrier function ( J:133680 )

• mice are refractory to SLIT2 prevention of endothelial leakiness caused by VEGF administration into the skin

muscle

abnormal diaphragm morphology ( J:208012 )

• E15.5 diaphragms show slightly disrupted vascular development in the diaphragm

Genotype
MGI:6458566

hm2

• Allelic Composition: Robo4^tm1Kzh/Robo4^tm1Kzh
• Genetic Background: Not Specified

cardiovascular system

increased angiogenesis ( J:294754 )

• increased angiogenic sprouting in gWAT when fed high-fat diet

• normal angiogenic sprouting in gWAt when fed regular chow

increased vasodilation ( J:294754 )

• in gWAT arteries after administering insulin when fed high-fat diet

growth/size/body

growth/size/body region phenotype ( J:294754 )

N • normal body, gastrocnemius muscle and gWAT mass when fed regular chow

N • normal gastrocnemius muscle mass when fed high-fat diet

decreased susceptibility to diet-induced obesity ( J:294754 )

• non-significant liver weight gain when fed high-fat diet

• increased adipocyte area and decreased adipocyte count in gWAT when fed high-fat diet

• normal body weight and gWAT mass gain when fed high-fat diet

homeostasis/metabolism

decreased susceptibility to diet-induced obesity ( J:294754 )

• non-significant liver weight gain when fed high-fat diet

• increased adipocyte area and decreased adipocyte count in gWAT when fed high-fat diet

• normal body weight and gWAT mass gain when fed high-fat diet

decreased circulating glucose level ( J:294754 )

• no increase in blood glucose level in GTT when fed high-fat diet

decreased fasting circulating glucose level ( J:294754 )

• compared to wildtype when fed high-fat diet

• normal fasted glucose level when fed regular chow

improved glucose tolerance ( J:294754 )

• no increased glucose area under curve (AUC) in GTT when fed high-fat diet

• no increase in blood glucose level in GTT when fed high-fat diet

enhanced exercise endurance ( J:294754 )

• increased treadmill time to exhaustion and distance travelled when fed normal chow

muscle

increased vasodilation ( J:294754 )

• in gWAT arteries after administering insulin when fed high-fat diet

Genotype
MGI:5562651

cn3

• 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

cn4

• 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