Phenotypes associated with this allele

• Allele Symbol: Eml1^heco
• Allele Name: heterotopic cortex
• Allele ID: MGI:5560734
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Eml1^heco/Eml1^heco	involves: C57BL/6 * NOR	MGI:5560742
hm2	Eml1^heco/Eml1^heco	involves: NOR	MGI:5560741
ot3	Eml1^heco/?	involves: CD-1	MGI:5648122

Genotype
MGI:5560742

hm1

• Allelic Composition: Eml1^heco/Eml1^heco
• Genetic Background: involves: C57BL/6 * NOR

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

nervous system

ectopic cortical neuron ( J:208031 )

• cortical heterotopia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital nervous system abnormality		DOID:2490		J:208031

Genotype
MGI:5560741

hm2

• Allelic Composition: Eml1^heco/Eml1^heco
• Genetic Background: involves: NOR

behavior/neurological

impaired spatial learning ( J:208031 )

• mice exhibit lower performance during task acquisition in the automated radial maze and increased errors in reaching the platform in a Morris water maze test at 7 months compared with wild-type mice

abnormal righting response ( J:208031 )

• one-day delay in development

abnormal locomotor behavior ( J:208031 )

• slower development of locomotion

abnormal locomotor activation ( J:208031 )

• delayed geotaxis reflexes

decreased locomotor activity ( J:208031 )

• decreased activity in a Y-maze only at 2 months

bradykinesia ( J:208031 )

• brady- and hypokinesia in severely affected mice

seizures ( J:208031 )

• 3 of 23 mice exhibit spontaneous seizures similar to pilocarpine-induced seizures

increased susceptibility to pharmacologically induced seizures ( J:208031 )

• pilocarpine-induced

myoclonus ( J:208031 )

• spontaneous myoclonic jerks associated with interrupted exploratory behavior at 4 to 5 weeks

• however, no epileptic seizures are observed at 8 to 12 weeks

nervous system

nervous system phenotype ( J:208031 )

N • mice exhibit normal afferent connections

seizures ( J:208031 )

• 3 of 23 mice exhibit spontaneous seizures similar to pilocarpine-induced seizures

increased susceptibility to pharmacologically induced seizures ( J:208031 )

• pilocarpine-induced

myoclonus ( J:208031 )

• spontaneous myoclonic jerks associated with interrupted exploratory behavior at 4 to 5 weeks

• however, no epileptic seizures are observed at 8 to 12 weeks

abnormal cortical intermediate zone morphology ( J:208031 )

• increased thickness at E17

enlarged brain ventricles ( J:208031 )

• discrete ventricular enlargement

• huge ventricular enlargement in severely affected mice

thickened cerebral cortex ( J:208031 )

• in heterotropia cortex layer II/III compared with homotopic areas

brain atrophy ( J:208031 )

• lateral cortical atrophy in severely affected mice

ectopic cortical neuron ( J:208031 )

• cortical heterotopia

• bilateral subcortical band heterotropia beneath the medial neocortex and extending from the frontal lobe to the occipital lobe

• variable severity

growth/size/body

decreased body size ( J:208031 )

• in severely affected mice

decreased body weight ( J:208031 )

• in severely affected mice

craniofacial

abnormal cranium morphology ( J:208031 )

• in severely affected mice

integument

delayed hair appearance ( J:208031 )

muscle

myoclonus ( J:208031 )

• spontaneous myoclonic jerks associated with interrupted exploratory behavior at 4 to 5 weeks

• however, no epileptic seizures are observed at 8 to 12 weeks

skeleton

abnormal cranium morphology ( J:208031 )

• in severely affected mice

vision/eye

delayed eyelid opening ( J:208031 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital nervous system abnormality		DOID:2490		J:208031

Genotype
MGI:5648122

ot3

• Allelic Composition: Eml1^heco/?
• Genetic Background: involves: CD-1

nervous system

increased neuron apoptosis ( J:211342 )

• at both early and late stages of corticogenesis, many actively dividing cells are abnormally positioned in the brain which is associated with increased cell death in cortices at E13

abnormal radial glial cell morphology ( J:211342 )

• fewer radial glial cells in mitosis are apparent at the ventricular lining

abnormal neuronal precursor proliferation ( J:211342 )

• misplaced progenitor cells in E13 brains, present outside the ventricular zones, continue to proliferate longer than wild-type cells

• total number of BrdU+ cells is greater and more cells remain in the cell cycle, particularly in the subventricular zone, intermediate zone and cortical plate

abnormal brain development ( J:211342 )

• mice exhibit early corticogenesis progenitor defects in the brain

• at P3, many Cux1+ neurons fail to reach cortical layers II-IV and are present in the heterotopia, however almost all Tbr1+ neurons have reached their final destination in layer VI above the heterotopia

• at P3, and to a lesser extent at P7, columns of Cux1+ neurons between the heterotopia and the cortex are still seen, whereas the migration of these neurons is already complete in wild-type mice, indicating a temporal delay in neurons reaching their destination

• however, neurons migrate at the same speed as wild-type neurons

abnormal cortical intermediate zone morphology ( J:211342 )

• ectopic proliferation in the intermediate zone during corticogenesis

• many highly proliferating neuronal cells born at E15.5 remain blocked in the lower intermediate zone

ectopic neuron ( J:211342 )

• mice present subcortical heterotopia in the rostromedial part of the neocortex close to the hippocampus

• by E17, both early-born, Tbr1+ and late-born, Cux1+ neurons (apical progenitors) contribute to heterotopia formation and disorganized radial glial cell processes are seen throughout the heteropia

• however, accumulation of heterotopic neurons is not seen at E15

cellular

abnormal mitotic spindle morphology ( J:211342 )

• most anaphase cells located at the ventricular lining show different cleavage orientations at E13 and E16 from the wild-type cells which show vertically oriented DNA, indicating abnormal spindle orientations

increased neuron apoptosis ( J:211342 )

• at both early and late stages of corticogenesis, many actively dividing cells are abnormally positioned in the brain which is associated with increased cell death in cortices at E13

abnormal radial glial cell morphology ( J:211342 )

• fewer radial glial cells in mitosis are apparent at the ventricular lining

abnormal neuronal precursor proliferation ( J:211342 )

• misplaced progenitor cells in E13 brains, present outside the ventricular zones, continue to proliferate longer than wild-type cells

• total number of BrdU+ cells is greater and more cells remain in the cell cycle, particularly in the subventricular zone, intermediate zone and cortical plate

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital nervous system abnormality		DOID:2490		J:211342