Phenotypes associated with this allele

• Allele Symbol: Nrp2^tm1.2Mom
• Allele Name: targeted mutation 1.2, Peter Mombaerts
• Allele ID: MGI:2183904
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nrp2^tm1.2Mom/Nrp2^tm1.2Mom	involves: 129P2/OlaHsd	MGI:5897106
hm2	Nrp2^tm1.2Mom/Nrp2^tm1.2Mom	involves: 129P2/OlaHsd * C57BL/6 * FVB/NJ	MGI:4843917
hm3	Nrp2^tm1.2Mom/Nrp2^tm1.2Mom	involves: 129P2/OlaHsd * C57BL/6 * SJL/J	MGI:3618513
ht4	Nrp2^tm1.2Mom/Nrp2^+	involves: 129P2/OlaHsd * C57BL/6 * FVB/NJ	MGI:4843918
cx5	Nrp2^tm1.2Mom/Nrp2^+ Sema3f^tm1.2Ddg/Sema3f^+	involves: 129P2/OlaHsd	MGI:5897107
cx6	Nrp2^tm1.2Mom/Nrp2^tm1.2Mom Vmn1r49^tm1Mom/Vmn1r49^tm1Mom	involves: 129P2/OlaHsd * C57BL/6J	MGI:3760744
cx7	Gucy2d^tm1Mom/Gucy2d^tm1Mom Nrp2^tm1.2Mom/Nrp2^tm1.2Mom	involves: 129P2/OlaHsd * C57BL/6J	MGI:3760743

Genotype
MGI:5897106

hm1

• Allelic Composition: Nrp2^tm1.2Mom/Nrp2^tm1.2Mom
• Genetic Background: involves: 129P2/OlaHsd

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

immune system

abnormal lymphatic vessel morphology ( J:226501 )

• decreased lymphatic branching complexity

abnormal lymphatic vessel endothelial cell morphology ( J:226501 )

• increased numbers which remain in lymph sac-like tubes near the cardinal vein

lymphatic vessel hyperplasia ( J:226501 )

• increased lymphatic width

• hyperplastic lymphatic vasculature in the back skin at E15.5, which remains defective at E17.5

abnormal lymphatic system physiology ( J:226501 )

• increased lymphatic endothelial cell proliferation at E14.5

Genotype
MGI:4843917

hm2

• Allelic Composition: Nrp2^tm1.2Mom/Nrp2^tm1.2Mom
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/NJ

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:166116 )

• all mutants treated with KA to induce seizures die within a week

postnatal lethality, incomplete penetrance ( J:166116 )

• some mice die in spontaneous status epilepticus between P7 and P21

behavior/neurological

seizures ( J:166116 )

increased susceptibility to pharmacologically induced seizures ( J:166116 )

• all mutants treated with kainic acid (KA) to induce seizures die within a week

environmentally induced seizures ( J:166116 )

• 12 of 51 mice exhibit random handling-induced seizures

myoclonus ( J:166116 )

• 12 of 51 mice exhibit random handling-induced seizures

muscle

myoclonus ( J:166116 )

• 12 of 51 mice exhibit random handling-induced seizures

nervous system

seizures ( J:166116 )

increased susceptibility to pharmacologically induced seizures ( J:166116 )

• all mutants treated with kainic acid (KA) to induce seizures die within a week

environmentally induced seizures ( J:166116 )

• 12 of 51 mice exhibit random handling-induced seizures

myoclonus ( J:166116 )

• 12 of 51 mice exhibit random handling-induced seizures

abnormal hippocampus neuron morphology ( J:166116 )

• mutants exhibit selective loss of GABAergic cells in the hippocampus

• Parv+ and NPY+ neurons are reduced in the hippocampus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:166116

Genotype
MGI:3618513

hm3

• Allelic Composition: Nrp2^tm1.2Mom/Nrp2^tm1.2Mom
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL/J

mortality/aging

prenatal lethality, incomplete penetrance ( J:76686 )

• homozygous mutant pups are born alive at a reduced frequency (10.9% vs expected 25%); however, no increased mortality is noted in juvenile or adult mice

nervous system

abnormal axon guidance ( J:76686 )

• homozygotes display aberrant axonal innervation of the main olfactory bulb and accessory olfactory bulb by olfactory sensory neurons and vomeronasal sensory neurons, respectively

abnormal vomeronasal sensory neuron morphology ( J:76686 )

• in the vomeronasal system, homozygotes exhibit axonal defasciculation within the vomeronasal nerve

hydrocephaly ( J:76686 )

• 63.6% of homozygotes exhibit hydrocephalus (not observed in heterozygotes)

abnormal sensory neuron innervation pattern ( J:76686 )

• in the vomeronasal system, some apical vomeronasal sensory neuron axons are misrouted and innervate glomeruli in an ectopic domain of the accessory olfactory bulb

abnormal olfactory neuron innervation pattern ( J:76686 )

• homozygotes display marked and distinct abnormalities on target innervation within the olfactory bulb

• in the main olfactory system, axons of mutant olfactory sensory neurons penetrate into the deeper layers of the main olfactory bulb, overshooting their glomerular target and extending into the external plexiform layer

abnormal vomeronasal sensory neuron physiology ( J:76686 )

• some apical vomeronasal sensory neuron axons are misrouted and innervate glomeruli in an ectopic domain of the accessory olfactory bulb

growth/size/body

abnormal vomeronasal sensory neuron morphology ( J:76686 )

• in the vomeronasal system, homozygotes exhibit axonal defasciculation within the vomeronasal nerve

postnatal growth retardation ( J:76686 )

• at P2-P3, mutant pups display a striking reduction of overall body size, resulting in ~50% of normal size at 3 weeks of age

• however, mutant mice catch up with their wild-type littermates at weaning, and exhibit a normal body size after 6-8 weeks

reproductive system

reduced fertility ( J:76686 )

• homozygotes often are not able to reproduce

respiratory system

abnormal vomeronasal sensory neuron morphology ( J:76686 )

• in the vomeronasal system, homozygotes exhibit axonal defasciculation within the vomeronasal nerve

craniofacial

abnormal vomeronasal sensory neuron morphology ( J:76686 )

• in the vomeronasal system, homozygotes exhibit axonal defasciculation within the vomeronasal nerve

cellular

abnormal axon guidance ( J:76686 )

• homozygotes display aberrant axonal innervation of the main olfactory bulb and accessory olfactory bulb by olfactory sensory neurons and vomeronasal sensory neurons, respectively

Genotype
MGI:4843918

ht4

• Allelic Composition: Nrp2^tm1.2Mom/Nrp2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/NJ

behavior/neurological

seizures ( J:166116 )

increased susceptibility to pharmacologically induced seizures ( J:166116 )

• 7 of 9 mutants treated with kainic acid (KA) to induce seizures, develop at least two spontaneous seizures that qualify as epilepsy

• mutants treated with KA to induce seizures exhibit a shorter latency to onset of seizures

• mutants treated with pentylenetretrazol (PTZ) to induce seizures exhibit a significantly shorter latency to onset of seizures than controls but exhibit a similar number of acute seizures as controls

environmentally induced seizures ( J:166116 )

• 14 of 273 mice exhibit random handling-induced seizures

myoclonus ( J:166116 )

• 14 of 273 mice exhibit random handling-induced seizures

muscle

myoclonus ( J:166116 )

• 14 of 273 mice exhibit random handling-induced seizures

nervous system

abnormal dendrite morphology ( J:166116 )

• moderate decrease in dendritic branching and total dendritic length of CA1 pyramidal cells

abnormal dendritic spine morphology ( J:166116 )

• N type and D type spines are increased 11% compared to CA1 neurons from wild-type

abnormal nervous system physiology ( J:166116 )

• mutants exhibit enhanced excitability in the hippocampus as indicated by an increase in population spike (PS) amplitude

seizures ( J:166116 )

increased susceptibility to pharmacologically induced seizures ( J:166116 )

• 7 of 9 mutants treated with kainic acid (KA) to induce seizures, develop at least two spontaneous seizures that qualify as epilepsy

• mutants treated with KA to induce seizures exhibit a shorter latency to onset of seizures

• mutants treated with pentylenetretrazol (PTZ) to induce seizures exhibit a significantly shorter latency to onset of seizures than controls but exhibit a similar number of acute seizures as controls

environmentally induced seizures ( J:166116 )

• 14 of 273 mice exhibit random handling-induced seizures

myoclonus ( J:166116 )

• 14 of 273 mice exhibit random handling-induced seizures

abnormal synaptic plasticity ( J:166116 )

• short-term plasticity is altered as indicated by a decrease in the facilitation of the secondary population spike (PS) elicited during the 7 Hz stimulation train

Genotype
MGI:5897107

cx5

• Allelic Composition: Nrp2^tm1.2Mom/Nrp2⁺; Sema3f^tm1.2Ddg/Sema3f⁺
• Genetic Background: involves: 129P2/OlaHsd

immune system

abnormal lymphatic vessel endothelial cell morphology ( J:226501 )

• increased numbers as much as in Sema3f^tm1.2Ddg homozygotes

Genotype
MGI:3760744

cx6

• Allelic Composition: Nrp2^tm1.2Mom/Nrp2^tm1.2Mom; Vmn1r49^tm1Mom/Vmn1r49^tm1Mom
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

nervous system

abnormal olfactory bulb morphology ( J:125485 )

• axonal projections exhibit defasciculation across the medial surface of the main olfactory bulb

Genotype
MGI:3760743

cx7

• Allelic Composition: Gucy2d^tm1Mom/Gucy2d^tm1Mom; Nrp2^tm1.2Mom/Nrp2^tm1.2Mom
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

nervous system

abnormal olfactory bulb morphology ( J:125485 )

• guanylate cyclase- D (GC-D) positive glomeruli fan out more than in wild-type mice and glomeruli form at inappropriate locations

• many GC-D+ glomeruli scatter ectopically across the main olfactory bulb up to the rostral tip

• fewer GC-D+ glomeruli are found in the necklace compared to in wild-type mice

• the number of GC-D+ glomeruli is increased compared to in wild-type mice

• Npr2+ axons erroneously project into the posterior accessory olfactory bulb