|
hm1
|
Fig4plt1/Fig4plt1
B6.Cg-Fig4plt1 |
|
|||||||||||||||||
|
• significant degeneration of the atria with large, transparent vacuoles
|
|
|
hm2
|
Fig4plt1/Fig4plt1
involves: 129 * C3H * C57BL/6J * CAST/Ei * SJL |
|
|||||||||||||||||
|
• survive to 1 -2 months of age
|
|
• extensive autophagic inclusion bodies
|
|
• thinning of the myelin sheath of the sciatic nerve
|
|
• thinning of the myelin sheath of the sciatic nerve
|
|
• in the sciatic nerve
|
|
• severe spongiform degeneration in the brain and extensive loss of neurons from the peripheral ganglia
|
|
• extensive loss of neurons from peripheral ganglia
• neurons in layers 4 and 5 of the cortex, the deep cerebellar nuclei, and the dorsal root ganglia are severely affected with accumulation of vacuoles that fill the cytoplasm
|
|
|
hm3
|
Fig4plt1/Fig4plt1
involves: 129P2/OlaHsd * C3H * C57BL/6 * CAST/Ei * SJL |
|
|||||||||||||||||
|
• all mice die by 6 weeks
(J:122737)
• juvenile lethality at 6-8 weeks of age
(J:185989)
|
|
• severe movement disorder by 30 days of age
|
|
• progressive loss of mobility
|
|
• at week 3
|
|
• mice have a 'swimming' gait
|
|
• at 6 weeks, spinal motor neurons accumulates vacuoles prior to cell loss
|
|
• visible at week 1, mice exhibit neonatal degeneration in sensory and autonomic ganglia with loss of neurons in from layers 4 and 5 of the cortex, deep cerebellar nuclei, thalamus, pons and medulla
|
|
• mice exhibit fewer large-diameter myelinated axons
• sciatic nerve conduction velocity is slowed
• sciatic nerves have reduced amplitude of compound muscle action potential
|
|
• reduced sciatic nerve myelination
• low abundance of myelin basic protein
|
|
• sciatic nerves have reduced amplitude of compound muscle action potential
|
|
• sciatic nerve conduction velocity is slowed
(J:122737)
• sciatic nerve conduction velocity reduced to 50% of velocity in control mice
(J:185989)
|
|
• in deep layers of cortex, cerebellar nuclei, hippocampus, brainstem, and dorsal root ganglia
|
|
• at P3
|
|
• severe tremors develop 2 weeks after birth
|
|
• severe tremors develop 2 weeks after birth
|
|
• at P3
(J:122737)
|
|
• clumps of melanosomes are visible in the few remaining pigmented hair follicles
|
|
• at P3
(J:122737)
|
|
• clumps of melanosomes are visible in the few remaining pigmented hair follicles
|
|
• pigment containing hair follicles are decreased in number
|
Mouse Models of Human Disease |
OMIM ID | Ref(s) | |
| Charcot-Marie-Tooth Disease, Type 4j; CMT4J | 611228 | J:122737 | |
|
|
cx4
|
Fig4plt1/Fig4plt1 Tg(ACTB-Fig4*I41T)705Mm/0 involves: 129 * C3H * C57BL/6J * CAST/Ei * SJL |
|
|||||||||||||||||
|
• survival is increased to 3?6 months compared to from 1?2 months in Fig4 null mice not carrying the transgene
|
| N |
• unlike in null mice not carrying the transgene, myelin sheath thinning is not seen
(J:173446)
|
|
• intermediate level of autophagic inclusion bodies
|
|
• high pressure hydrocephalus is indicated by the compression of the cerebellum and hippocampus
|
|
• intermediate level compared to null mice not carrying the transgene
|
|
• reduced at 4 and 14 months of age in the sciatic nerve but not as much as in null mice not carrying the transgene
|
|
• intermediate level of degeneration compared to null mice not carrying the transgene
• degeneration of the cerebellar nuclei
|
Mouse Models of Human Disease |
OMIM ID | Ref(s) | |
| Charcot-Marie-Tooth Disease, Type 4j; CMT4J | 611228 | J:173446 | |
|
|
cx5
|
Fig4plt1/Fig4plt1 Tg(ACTB-Fig4*I41T)721Mm/0 involves: 129 * C3H * C57BL/6J * CAST/Ei * SJL |
|
|||||||||||||||||
| N |
• survival is completely corrected compared to Fig4 null mice not carrying the transgene
(J:173446)
|
| N |
• unlike in null mice not carrying the transgene, myelin sheath thinning is not seen
(J:173446)
|
|
• a few autophagic inclusion bodies are present
|
|
• astrocytosis is almost completely corrected compared to null mice not carrying the transgene
|
|
• reduced at 4 and 14 months of age in the sciatic nerve but not as much as in null mice not carrying the transgene
|
|
• minimal spongiform degeneration unlike in null mice not carrying the transgene
• unlike in null mice not carrying the transgene, dorsal root ganglia are intact at P90
• degeneration of the cerebellar nuclei
|
|
• minimal
|
|
• partial rescue of reduced pigmentation compared to null mice not carrying the transgene
|
|
|
cx6
|
Fig4plt1/Fig4plt1 Tg(Eno2-Fig4)#Mm/? involves: 129P2/OlaHsd * C3H * C57BL/6 * CAST/Ei * SJL |
|
|||||||||||||||||
|
• 65% of mice live 10 months or more
|
|
• growth rate is improved during the first month relative to Fig4plt1 homozygotes
|
| N |
• spongiform degeneration corrected at 3 weeks of age and in mice 9 and 12 months old
(J:185989)
• dorsal root ganglion spongiform degeneration also improved
(J:185989)
• sciatic nerve conduction velocity normal
(J:185989)
• normal sciatic nerve myelination
(J:185989)
|
|
|
cx7
|
Fig4plt1/Fig4plt1 Tg(GFAP-Fig4)#Mm/? involves: 129P2/OlaHsd * C3H * C57BL/6 * CAST/Ei * SJL |
|
|||||||||||||||||
|
• survival not corrected relative to Fig4plt1 homozygotes
|
|
• growth not corrected relative to Fig4plt1 homozygotes
|
|
• severe movement disorder by 30 days of age
|
| N |
• astrogliosis mostly corrected
(J:185989)
|
|
• reduced sciatic nerve myelination
• low abundance of myelin basic protein
|
|
• extensive
|