Mouse Genome Informatics
hm1
    Nrp2tm1.2Mom/Nrp2tm1.2Mom
involves: 129P2/OlaHsd * C57BL/6 * FVB/NJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mutants treated with KA to induce seizures die within a week
• some mice die in spontaneous status epilepticus between P7 and P21

behavior/neurological
• all mutants treated with kainic acid (KA) to induce seizures die within a week
• 12 of 51 mice exhibit random handling-induced seizures
• 12 of 51 mice exhibit random handling-induced seizures

muscle
• 12 of 51 mice exhibit random handling-induced seizures

nervous system
• all mutants treated with kainic acid (KA) to induce seizures die within a week
• 12 of 51 mice exhibit random handling-induced seizures
• 12 of 51 mice exhibit random handling-induced seizures
• mutants exhibit selective loss of GABAergic cells in the hippocampus
• Parv+ and NPY+ neurons are reduced in the hippocampus

Mouse Models of Human Disease
OMIM IDRef(s)
Autism 209850 J:166116


Mouse Genome Informatics
hm2
    Nrp2tm1.2Mom/Nrp2tm1.2Mom
involves: 129P2/OlaHsd * C57BL/6 * SJL/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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
• homozygotes display aberrant axonal innervation of the main olfactory bulb and accessory olfactory bulb by olfactory sensory neurons and vomeronasal sensory neurons, respectively
• in the vomeronasal system, homozygotes exhibit axonal defasciculation within the vomeronasal nerve
• 63.6% of homozygotes exhibit hydrocephalus (not observed in heterozygotes)
• in the vomeronasal system, some apical vomeronasal sensory neuron axons are misrouted and innervate glomeruli in an ectopic domain of the accessory olfactory bulb
• 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

growth/size
• in the vomeronasal system, homozygotes exhibit axonal defasciculation within the vomeronasal nerve
• 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
• homozygotes often are not able to reproduce

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

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

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


Mouse Genome Informatics
ht3
    Nrp2tm1.2Mom/Nrp2+
involves: 129P2/OlaHsd * C57BL/6 * FVB/NJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 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
• 14 of 273 mice exhibit random handling-induced seizures
• 14 of 273 mice exhibit random handling-induced seizures

muscle
• 14 of 273 mice exhibit random handling-induced seizures

nervous system
• moderate decrease in dendritic branching and total dendritic length of CA1 pyramidal cells
• N type and D type spines are increased 11% compared to CA1 neurons from wild-type
• mutants exhibit enhanced excitability in the hippocampus as indicated by an increase in population spike (PS) amplitude
• 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
• 14 of 273 mice exhibit random handling-induced seizures
• 14 of 273 mice exhibit random handling-induced seizures
• 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


Mouse Genome Informatics
cx4
    Gucy2dtm1Mom/Gucy2dtm1Mom
Nrp2tm1.2Mom/Nrp2tm1.2Mom

involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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


Mouse Genome Informatics
cx5
    Nrp2tm1.2Mom/Nrp2tm1.2Mom
Vmn1r49tm1Mom/Vmn1r49tm1Mom

involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• axonal projections exhibit defasciculation across the medial surface of the main olfactory bulb