Phenotypes Associated with This Genotype

Genotype
MGI:5490471

• Allelic Composition: Vps54^wr/Vps54^wr
• Genetic Background: involves: C57BL/6J * C57BL/Fa

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

nervous system

increased microglial cell activation ( J:181019 )

• microglia activation accompanies motor neuron degeneration

gliosis ( J:181019 )

• reactive gliosis accompanies motor neuron degeneration

abnormal GABAergic neuron morphology ( J:181019 )

• decrease in density of parvalbumin-positive neurons in layer 5 of the primary motor cortex

• decrease in density of somatostatin-positive neurons in layer 5 of the primary motor cortex

• decrease in optical density of GABAergic synaptic boutons as assessed by VGAT staining in layer 5 of the primary motor cortex

motor neuron degeneration ( J:181019 )

abnormal synaptic bouton morphology ( J:181019 )

• decrease in optical density of GABAergic synaptic boutons as assessed by VGAT staining in layer 5 of the primary motor cortex

abnormal GABAergic neuron physiology ( J:181019 )

• layer 5 pyramidal neurons exhibit increased excitability as a result of decreased GABAergic inhibition

abnormal GABA-mediated receptor currents ( J:181019 )

• mutant mice exhibit a down regulation in phasic and tonic GABA(a) receptor-mediated currents

• mice exhibit an 87% reduction in average tonic current densities (pA/pF) as compared to controls

• input resistance in layer 5 pyramidal neurons is increased in mutant mice as compared to controls

• current threshold is significantly lower in mutant mice, however polarization voltage is similar between mutant and control

abnormal inhibitory postsynaptic currents ( J:181019 )

• individual spontaneous inhibitory post synaptic currents (sIPSC) display smaller amplitudes, however mean amplitude is not statistically different in whole-cell voltage-clamp recordings from layer 5 pyramidal neurons

• sIPSC frequency is 28% lower than controls

abnormal miniature inhibitory postsynaptic currents ( J:181019 )

• whole cell recordings of miniature IPSC (mIPSC) in layer 5 pyramidal neurons detect an increase in weighted decay time constant, but no differences in amplitude or rise time

decreased miniature inhibitory postsynaptic current frequency ( J:181019 )

• mIPSC frequency is 36% lower than controls

muscle

progressive muscle weakness ( J:181019 )

• mice develop muscle weakness in the forelimbs beginning at 3-4 weeks

immune system

increased microglial cell activation ( J:181019 )

• microglia activation accompanies motor neuron degeneration

hematopoietic system

increased microglial cell activation ( J:181019 )

• microglia activation accompanies motor neuron degeneration

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:181019 , J:196432