Phenotypes associated with this allele

• Allele Symbol: Pmp22^Tr-J
• Allele Name: trembler Jackson
• Allele ID: MGI:1856217
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pmp22^Tr-J/Pmp22^Tr-J	involves: C57BL/6	MGI:3794281
ht2	Pmp22^Tr-J/Pmp22^+	B6.Cg-Pmp22^Tr-J Krt25^Re/+ +/J	MGI:3794294
ht3	Pmp22^Tr-J/Pmp22^+	involves: C57BL/6	MGI:3794288
ot4	Pmp22^Tr-J/?	involves: C57BL/6J	MGI:3794279

Genotype
MGI:3794281

hm1

• Allelic Composition: Pmp22^Tr-J/Pmp22^Tr-J
• Genetic Background: involves: C57BL/6

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

mortality/aging

decreased survivor rate ( J:7945 )

• most mice die by day 18

postnatal lethality ( J:7945 )

• most mice die by day 18

behavior/neurological

abnormal motor coordination/balance ( J:7945 )

• mice are noticeably disabled at day 8 and progressively worsen such that they have a difficult time walking

Genotype
MGI:3794294

ht2

• Allelic Composition: Pmp22^Tr-J/Pmp22⁺
• Genetic Background: B6.Cg-Pmp22^Tr-J Krt25^Re/+ +/J

nervous system

demyelination ( J:101812 )

• at 72 days, mice exhibit severe hypomyelination and the number of myelinated nerves is decreased compared to in wild-type mice

• 'onion bulb' formations are evidence of repetitive cycles of demyelination and remyelination

abnormal action potential ( J:101812 )

• at 30 days of age, compound muscle action potential (CMAP) amplitude is reduced 85%, distal motor latency is prolonged 112%, conduction velocity is reduced 81%, and CMAP duration is increased 253% compared to in wild-type mice

• at 72 days of age, CMAP amplitude is reduced 87%, distal motor latency is prolonged 77%, conduction velocity is reduced 72%, and CMAP duration is increased 326% compared to in wild-type mice

cellular

abnormal cell physiology ( J:97015 )

• proteosome activity is impaired

abnormal autophagy ( J:119095 )

• autophagy is induced in neuropathic mouse nerves unlike in wild-type mice

• however, experimentally induced autophagy and or/ chaperones hinders Pmp22 protein aggregation

homeostasis/metabolism

abnormal autophagy ( J:119095 )

• autophagy is induced in neuropathic mouse nerves unlike in wild-type mice

• however, experimentally induced autophagy and or/ chaperones hinders Pmp22 protein aggregation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Charcot-Marie-Tooth disease type 1A		DOID:0110148	OMIM:118220	J:3394 , J:101812

Genotype
MGI:3794288

ht3

• Allelic Composition: Pmp22^Tr-J/Pmp22⁺
• Genetic Background: involves: C57BL/6

nervous system

abnormal Schwann cell morphology ( J:39953 , J:134811 )

• Schwann cell nuclei numbers are increased (J:39953)

• Shwann cell numbers and rates of apoptosis are increased compared to in wild-type mice (J:134811)

• however, treatment with curcumin decreases apoptosis rates of Schwann cells (J:134811)

abnormal axon morphology ( J:134811 )

• treatment with curcumin increases axonal size

abnormal dorsal root ganglion morphology ( J:39953 )

• mice exhibit minor structural changes in dorsal root ganglion cells

abnormal myelination ( J:39953 , J:98231 )

• 40% to 60% of axons lack myelination (J:39953)

behavior/neurological

impaired coordination ( J:134811 )

• mice are unable to remain on a rotarod as long as wild-type mice

• however, treatment with curcumin improves coordination

abnormal gait ( J:39953 )

• beginning at 4 to 6 weeks of age, mice exhibit abnormal gait with hindlimb spaying

muscle

muscle degeneration ( J:39953 )

• mice exhibit muscle wasting

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Charcot-Marie-Tooth disease type 1A		DOID:0110148	OMIM:118220	J:3394 , J:98231

Genotype
MGI:3794279

ot4

• Allelic Composition: Pmp22^Tr-J/?
• Genetic Background: involves: C57BL/6J

nervous system

abnormal Schwann cell morphology ( J:7222 )

• Schwann cells are delayed or fail to ensheath axons as in wild-type mice

increased Schwann cell number ( J:76795 )

decreased myelin sheath thickness ( J:76795 )

• g ratio of Schwann cells is increased, indicating thin myelin sheaths

axon degeneration ( J:76795 )

• axonal degeneration at 8 months of age

abnormal myelination ( J:7222 )

• mice exhibit mild deficiencies in myelin at the sciatic and vagus nerves compared to in wild-type but not as severe as in Pmp22^Tr mice

dysmyelination ( J:76795 )

• 18.4% of fibers are dysmyelinated

• however, myelin periodicity is normal

behavior/neurological

tremors ( J:7222 )

• beginning at P20 to P25

abnormal gait ( J:7222 )

• mice exhibit milder gait abnormalities than in Pmp22^Tr mice