Phenotypes Associated with This Genotype

Genotype
MGI:5478744

• Allelic Composition: Tg(CMV-LITAF*W116G)#Lli/Tg(CMV-LITAF*W116G)#Lli
• Genetic Background: FVB-Tg(CMV-LITAF*W116G)#Lli

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

behavior/neurological

abnormal behavior ( J:194981 )

• mutants occasionally self-mutilate their tails which may be possible evidence of paresthesia

hyporesponsive to tactile stimuli ( J:194981 )

• mutants perform worse than controls in the tail-flick test indicating impaired sensory function

limb grasping ( J:194981 )

• mutants show abnormal clenching of toes and clasping of hind limbs upon tail suspension at 1 year of age, with some flexing all four limbs and even their whole body

impaired coordination ( J:194981 )

• mutants show impaired motor performance after the 4th trial of the rotarod test

nervous system

abnormal axon morphology ( J:194981 )

• axon contours of sciatic nerves are less circular and axon caliber and axon area are smaller than in controls

• axons with myelin infoldings are often displaced, deformed, or constricted

abnormal juxtaparanode morphology ( J:194981 )

• segregation of the paranodal and juxtaparanodal compartments is disrupted in axons, with 73% of nodes of Ranvier in sciatic nerves having a paranode-juxtaparanode overlap phenotype

abnormal myelin sheath morphology ( J:194981 )

• 1 year old mutants exhibit peripheral nerves with abnormal Schwann cell-axon units with focally infolded myelin sheaths that appear as single, double, or triple internal myelin rings within a myelinated axon

abnormal node of Ranvier morphology ( J:194981 )

• nodes of Ranvier with myelin infolding often show paranodal retraction leading to a larger nodal gap

• nodal gap length of sciatic nerves is longer than in controls

abnormal paranode morphology ( J:194981 )

• segregation of the paranodal and juxtaparanodal compartments is disrupted in axons, with 73% of nodes of Ranvier in sciatic nerves having a paranode-juxtaparanode overlap phenotype

• accumulation of electron-dense organelles, mainly mitochondria, in the axoplasm of the paranodal region next to the infolded myelin

• presence of myelin infoldings at the paranodal regions and these regions often show signs of dys/demyelination and axonal damage

• non-compacted myelin whorls extend from the compact myelin into the axon, suggesting loss of myelin compaction at the paranodal region

abnormal sciatic nerve morphology ( J:194981 )

• sciatic nerves from 12-15 month old mutants exhibit abundant myelin abnormalities with focally folded structures

axon degeneration ( J:194981 )

• small but significant increase in the percentage of sciatic nerves undergoing axonal degeneration at 12-15 months of age

abnormal myelination ( J:194981 )

• non-compacted myelin whorls extend from the compact myelin into the axon, suggesting loss of myelin compaction at the paranodal region

• peripheral nerve dysmyelination with myelin infolding

• myelin infolding is specific to peripheral nerves and is seen in motor and sensory nerves; infoldings are more prominent in sciatic nerves than in ventral or dorsal roots

• infolded myelin loops originate from the myelin sheath at the paranodal regions and the internodal regions adjacent to Schmidt-Lanterman incisures

• occasionally, loss of myelin compaction and widened spacing of the Schmidt-Lanterman incisures are seen

• myelin infoldings precede axonal defects (nodal disorganization) in sciatic nerves

demyelination ( J:194981 )

• small but significant increase in the percentage of sciatic nerves with demyelinated axons at 12-15 months of age

• paranodal regions with myelin infolding often show signs of dys/demyelination and axonal damage

abnormal action potential ( J:194981 )

• compound muscle action potential amplitudes are reduced at 1 year of age, but not at 3 months

• sensory nerve action potentials could not be evoked in 2 of 11 mutants

decreased nerve conduction velocity ( J:194981 )

• motor nerve and tail sensory nerve conduction velocity are reduced at 1 year of age, but not 3 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Charcot-Marie-Tooth disease type 1C		DOID:0110151	OMIM:601098	J:194981