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Phenotypes Associated with This Genotype
Genotype
MGI:5690112
Allelic
Composition
Gdap1tm1.2Geno/Gdap1tm1.2Geno
Genetic
Background
involves: 129 * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gdap1tm1.2Geno mutation (0 available); any Gdap1 mutation (16 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• abnormal hind-limb clasping reflex at 3 months of age
• mice show reduced latency to fall on the rotarod at 3 months of age
• during locomotion, most mice show very low position of the body and dragging tail
• mice show more narrow gait angles and shorter stride length at 5 and 12 months of age
• 12 month old mice show a decrease of toe spreading and an increase in extension of plantar length during locomotion
• shorter stride length in 5 and 12 months old mice

nervous system
• embryonic motor neuron cultures show reduced axon length growth at 48 hours
• embryonic motor neuron cultures show reduced axon length growth at 48 hours
• cultured motor neurons show abnormal organelles structures including larger mitochondria and increased numbers of various sized vacuoles
• mitochondrial interconnectivity is reduced in the proximal segment of motor neuron axons after 24 and 48 hours in culture
• motor neurons in the anterior horn show cell lesions such as vacuoles and chromatolysis at 5 and 12 months of age
• motor neuron degeneration in the anterior horn occurs in the first months of life
• however, mice do not show a reduction in axonal number or myelin thickness and distribution of axon sizes in both proximal and distal sciatic nerves is normal
• dorsal root ganglia sensory neurons from 5 month old mice generate neurites with reduced average length when grown in culture
• occupancy of neuromuscular junctions (percentage of postsynaptic buttons that are completely filled by the nerve terminal) is reduced in 12 month old, but not 5 month old, mice
• muscles show abnormal tangle-like structures at terminal axons close to the neuromuscular junction
• motor neurons in the anterior horn show cell lesions such as vacuoles and chromatolysis at 5 and 12 months of age
• dorsal root ganglia sensory neurons from 5 month old mice generate neurites with reduced average length when grown in culture
• 5 month old, but not 2 month old, mice show a reduction of compound muscle action potential amplitude for distal (at the ankle) and proximal (at the hip) stimulation, indicating axonal neuropathy
• 5 month old mice show a slight but significant reduction in motor nerve conduction velocity
• the number of mitochondria is increased at 24 hours in culture in the proximal segment of motor neuron axons, indicating a delay of mitochondrial distribution along the axon which normalized by 48 hours in culture

homeostasis/metabolism
• cultured motor neurons show reduced cytosolic calcium and reduction in calcium inflow through store-operated calcium entry upon mobilization of endoplasmic reticulum (ER) calcium by thapsigargin
• motor neurons also show slow entrance velocity of calcium into the neuron and slow entry of calcium after store calcium depletion
• neurons show a lower increase of cytoplasmic calcium when treated with ionomycin to release calcium from cellular stores

limbs/digits/tail
• some mice show everted paws

cellular
• cultured embryonic motor neurons show changes in ER cristernae
• cultured motor neurons show larger and abnormal mitochondria
• embryonic motor neuron cultures show reduced axon length growth at 48 hours

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Charcot-Marie-Tooth disease axonal type 2K DOID:0110167 OMIM:607831
J:224701


Contributing Projects:
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
05/10/2022
MGI 6.19
The Jackson Laboratory