Phenotypes Associated with This Genotype

Genotype
MGI:5460859

• Allelic Composition: Fgd4^tm1.1Ics/Fgd4^tm1.1Ics
• Genetic Background: Not Specified

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

nervous system

abnormal myelin sheath morphology ( J:190437 )

• peripheral nerves show aberrant myelin during early steps of myelination and in myelin maintenance, including myelin infoldings and outfoldings of various complexities, redundant myelin loops, degradation of myelin and signs of demyelination and remyelination, both around nodes of Ranvier and Schmidt-Lanterman incisures

• mutants at P5 already show aberrant myelin structures in the sciatic nerve

• peripheral nerves of older mice show axons without myelin or with abnormally thin myelin, indicating demyelination and incomplete remyelination

abnormal myelination ( J:190437 )

• early onset of progressive dysmyelinating and demyelinating peripheral neuropathy, with distal nerve fibers more affected than proximal ones (distally accentuated neuropathy); sensory and motor fibers are affected

• mutants show more fibers with aberrant myelin structures from P14 to 80 weeks of age, with 6% of fibers affected at 2 weeks and reaching 40% by 80 weeks

demyelination ( J:190437 )

• early onset of progressive dysmyelinating and demyelinating peripheral neuropathy, with distal nerve fibers more affected than proximal ones (distally accentuated neuropathy); sensory and motor fibers are affected

• steep rise in demyelination/remyelination between 60 and 80 weeks of age

abnormal nervous system electrophysiology ( J:190437 )

• motor fibers of 60 week old mutants exhibit a moderate increase in distal latencies and a mild increase in F-wave latencies, reduction in nerve conduction velocity and dispersed compound muscle action potentials with mildly reduced amplitudes

abnormal action potential ( J:190437 )

• motor fibers of 60 week old mutants exhibit dispersed compound muscle action potentials with mildly reduced amplitudes

decreased nerve conduction velocity ( J:190437 )

• motor fibers of 60 week old mutants exhibit a reduction in nerve conduction velocity

behavior/neurological

decreased grip strength ( J:190437 )

• 60 week old mutants show mildly impaired grip strength

• however, rotarod performance and footprint analysis are normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Charcot-Marie-Tooth disease type 4H		DOID:0110192	OMIM:609311	J:190437