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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• motor neuron axons fail to form discrete ventral roots as they exit the spinal cord
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• mice exhibit improper motor neuron column formation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit abnormal motor neuron column formation at the lumbar level of the spinal cord
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit motor neuron axons that project aberrantly shortly after exiting the lumbar spinal cord
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit severe motor neuron axon guidance defects proximal to the spinal cord
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• growth cones fail to exhibit the normal phases of outgrowth
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• the intercostals motor nerves are reduced in thickness compared to in wild-type mice likely due to reduced numbers of axons present at the nerve
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• all mice exhibit severe projection errors in the ventral root with highly fluorescent GFP puncta at the thoracic and lumbar levels of the spinal cord
• mice exhibit limb innervation defects
• branchial motor neuron axons misproject from the ventral root and inappropriately enter the dorsal root ganglion
• lumbar motor neuron axons wander or stall within 100 um of exiting the spinal cord
• upper thoracic motor neuron axons exhibit stalling and misprojection
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• sensory neurons are thinner than in wild-type mice
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• sensory neuron axons are overgrown and defasciculated resulting in thinner nerves at more distal locations compared to in wild-type mice
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• the ventral ramus at the thoracic level is reduced in size while the posterior ramus is more prominent
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• growth cones fail to exhibit the normal phases of outgrowth
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit motor neuron axon misprojections specifically at the thoracic level of the spinal cord
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit motor neuron axon misprojections specifically at the thoracic level of the spinal cord
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• approximately 90% penetrance of abducens nerve hypoplasia
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• oculomotor nerve superior branch axons terminate prematurely within a bulb with a penetrance of 90%
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• extraocular muscle hypoplasia begins after P0, several days after extraocular muscle innervation is reduced, with normal position and size of the superior rectus and superior rectus muscles at E14.5
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• oculomotor nerve neurons show increased apoptosis from E12.5-E15.5
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• oculomotor nerve neurons show failure of axon elongation to the orbit; this nerve growth failure precedes motor neuron apoptosis
• developing axons of the oculomotor nerves superior division stall in the proximal nerve, and the growth cones enlarge, extend excessive filopodia, and assume random trajectories while inferior division axons reach the orbit but branch ectopically
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• oculomotor explant axons have normal growth but enlarged growth cones and increased filopodia
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• the distal abducens nerves appear thin at E12.5 and are thinner at E15.5
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• oculomotor nerve superior branch axons terminate prematurely within a bulb; the bulb contains misdirected axons with enlarged growth cones and increased number of filopodia and degenerating axons
• the developing distal oculomotor nerve superior division is hypoplastic while the inferior division develops aberrant branches
• the oculomotor nerve distal sections contain 55% fewer axons than proximal sections, and the proximal sections contain 18% fewer axons than wild-type proximal sections
• oculomotor nerve pathology does not arise from a primary defect in extraocular muscle development, axon retraction, or motor neuron cell death
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• thinning of distal oculomotor nerves at E11.5
• the developing oculomotor nerves superior division is thinner than that of wild-type mice, while the oculomotor nerves inferior division appears moderately thinner, with premature fasciculation into transient aberrant branches
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• extraocular muscle hypoplasia begins after P0, several days after extraocular muscle innervation is reduced, with normal position and size of the superior rectus and superior rectus muscles at E14.5
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• oculomotor nerve neurons show increased apoptosis from E12.5-E15.5
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• oculomotor nerve neurons show failure of axon elongation to the orbit; this nerve growth failure precedes motor neuron apoptosis
• developing axons of the oculomotor nerves superior division stall in the proximal nerve, and the growth cones enlarge, extend excessive filopodia, and assume random trajectories while inferior division axons reach the orbit but branch ectopically
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| congenital fibrosis of the extraocular muscles | DOID:0080143 |
OMIM:PS135700 |
J:213171 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• abducens nerve stalls and fails to innervate the lateral rectus and is absent from the orbit at E16.5
• oculomotor nerve aberrantly innervates the lateral rectus muscle, indicating compensatory innervation
• however, oculomotor nerve has a normal trajectory to the orbit
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• the number of abducens motor neurons is greatly reduced by E13.5, but is normal at E10.5, immediately prior to abducens stalling, indicating secondary motor neuron apoptosis by E13.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 90% of oculomotor nerves have mild proximal thickening in the absence of a bulb, distal thinning, hypoplasia of the oculomotor nerve superior division and a smaller oculomotor nerve inferior division
• about 30% of distal oculomotor nerves have aberrant, long, fasciculated branches that emerge from the oculomotor nerve inferior division exploratory region
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• E11.5 embryos show severe malformations of the hindbrain, with loss of rhombomeres 5 and 6
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• embryos show aberrant extraocular muscle innervation
• by E12.5, an aberrant branch of the oculomotor nerve forms and contacts the developing lateral rectus muscle along the normal abducens nerve trajectory and other aberrant branches develop and contact the retractor bulbi muscle
• at E13.5, the oculomotor nerve forms a second, more distal aberrant branch that extends toward the lateral rectus muscle in addition to the more proximal aberrant branches contacting the lateral rectus and retractor bulbi muscles
• by E16.5, the lateral rectus muscle receives innervation form the distinct proximal and distal aberrant oculomotor nerve branches
• the diameter of the distal aberrant branch of the oculomotor nerve is greater than that of the proximal aberrant branch
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• abducens nerves are missing in E11.5 embryos
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• E11.5 embryos show fusion of the glossopharyngeal and vagus nerves
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• oculomotor nerve forms aberrant branches that contact the retractor bulbi and lateral rectus muscles at E12.5 to E16.5
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Duane retraction syndrome | DOID:12557 |
OMIM:126800 OMIM:604356 |
J:237642 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• by E12.5, aberrant branches of the oculomotor nerve begin to form in the direction of the lateral rectus muscle and retractor bulbi muscle
• at E13.5, the oculomotor nerve forms a second, more distal aberrant branch that extends toward the lateral rectus muscle in addition to the more proximal aberrant branches contacting the lateral rectus and retractor bulbi muscles
• by E16.5, the abducens nerve remains hypoplastic but provides some innervation to the lateral rectus muscle
• by E16.5, the lateral rectus muscle receives innervation form the distinct proximal and distal aberrant oculomotor nerve branches
• the diameter of the distal aberrant branch of the oculomotor nerve is greater than that of the proximal aberrant branch
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• E11.5 embryos show hypoplastic abducens nerves
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Duane retraction syndrome | DOID:12557 |
OMIM:126800 OMIM:604356 |
J:237642 | |
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/30/2024 MGI 6.23 |
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