Mouse Genome Informatics
hm1
    Pmp22Tr-J/Pmp22Tr-J
involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• most mice die by day 18
• most mice die by day 18

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


Mouse Genome Informatics
ht2
    Pmp22Tr-J/Pmp22+
B6.Cg-Pmp22Tr-J Krt25Re/+ +/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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
• 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
• proteosome activity is impaired
• autophagy is induced in neuropathic mouse nerves unlike in wild-type mice
• however, experimentally induced autophagy and or/ chaperones hinders Pmp22 protein aggregation


Mouse Genome Informatics
ht3
    Pmp22Tr-J/Pmp22+
involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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)
• treatment with curcumin increases axonal size
• mice exhibit minor structural changes in dorsal root ganglion cells
• 40% to 60% of axons lack myelination (J:39953)

behavior/neurological
• mice are unable to remain on a rotarod as long as wild-type mice
• however, treatment with curcumin improves coordination
• beginning at 4 to 6 weeks of age, mice exhibit abnormal gait with hindlimb spaying

muscle
• mice exhibit muscle wasting


Mouse Genome Informatics
ot4
    Pmp22Tr-J/?
involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• Schwann cells are delayed or fail to ensheath axons as in wild-type mice
• mice exhibit mild deficiencies in myelin at the sciatic and vagus nerves compared to in wild-type but not as severe as in Pmp22Tr mice

behavior/neurological
• beginning at P20 to P25
• mice exhibit milder gait abnormalities than in Pmp22Tr mice