Phenotypes Associated with This Genotype

Genotype
MGI:5141091

• Allelic Composition: Tg(NEFL*E397K)#Milg/0
• Genetic Background: Not Specified

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

behavior/neurological

limb grasping ( J:173771 )

• when lifted by the tail, mutants are unable to spread their hind limbs, the lower joints appear stiff, and the digits of the hind limb curl instead of spreading

abnormal limb posture ( J:173771 )

• aberrant hindlimb posture

decreased locomotor activity ( J:173771 )

• mutants show reduced levels of voluntary locomotor activity relative to mice expressing the wild-type human NEFL on nights 3-5 of observation

• total distance run in a running wheel over the course of a week is reduced compared to controls

paraparesis ( J:173771 )

• signs of hind limb weakness as seen as early as 4 months of age

limbs/digits/tail

abnormal digit morphology ( J:173771 )

• digit abnormalities as seen as early as 4 months of age

muscle

muscular atrophy ( J:173771 )

• mutants exhibit progressive muscle atrophy in the hind limbs without signs of muscle denervation by 6 months of age

nervous system

abnormal motor neuron morphology ( J:173771 )

• ectopic accumulation of phosphorylated neurofilaments in motor neuron cell bodies as early as 1 month of age

• neurofilament organization is also altered in motor and sensory roots, with small motor axons affected the most

abnormal axon morphology ( J:173771 )

• peak axonal diameter is reduced for small motor axons before and after the onset of symptoms, whereas large motor axons are affected only after the onset of symptoms

abnormal spinal cord ventral horn morphology ( J:173771 )

• ectopic neurofilaments accumulate in NEFL positive cells within the ventral horn at 1 and 3 months of age and persist in 6 and 13 month old mutants

decreased nerve conduction velocity ( J:173771 )

• mutants exhibit reduced motor nerve conduction velocities in the sciatic nerve

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Charcot-Marie-Tooth disease type 2E		DOID:0110165	OMIM:607684	J:173771