Phenotypes associated with this allele
Allelic
Composition |
Plp1tm1Kan/Plp1+
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Genetic
Background |
involves: 129S1/Sv * 129X1/SvJ |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Plp1tm1Kan mutation
(1 available);
any
Plp1 mutation
(19 available)
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nervous system
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• axonal swelling and degeneration are seen but less frequently than in hemizygous males; however all optic nerve axons have normal myelin sheaths
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Plp1tm1Kan mutation
(1 available);
any
Plp1 mutation
(19 available)
Tspan2tm1Hbw mutation
(0 available);
any
Tspan2 mutation
(11 available)
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nervous system
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• increased density of microglia in the hippocampal fimbria
• microglial cells appear to be phagocytic based on presence of inflated lysosomes
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• infiltration of cytotoxic T cells and macrophages in the hippocampal fimbria
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• severe reactive astrogliosis in the hippocampal fimbria
• enhanced compared to single mutants
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• similar to what is seen in mice hemizygous for Plp1tm1Kan alone
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• similar to what is seen in mice hemizygous for Plp1tm1Kan alone
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• moderately dysmyelinated, similar to what is seen in mice hemizygous for Plp1tm1Kan alone
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behavior/neurological
growth/size/body
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• at 4 and 40 weeks of age
• similar to what is seen in mice hemizygous for Plp1tm1Kan alone
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skeleton
immune system
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• increased density of microglia in the hippocampal fimbria
• microglial cells appear to be phagocytic based on presence of inflated lysosomes
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• infiltration of cytotoxic T cells and macrophages in the hippocampal fimbria
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hematopoietic system
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• increased density of microglia in the hippocampal fimbria
• microglial cells appear to be phagocytic based on presence of inflated lysosomes
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cnptm1(cre)Kan mutation
(0 available);
any
Cnp mutation
(26 available)
Plp1tm1Kan mutation
(1 available);
any
Plp1 mutation
(19 available)
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hematopoietic system
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• density of T-lymphocytes (CD3+ cells) in the fimbria is further increased at 26 weeks of age compared to single hemizygous Plp1 males
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• microgliosis in the hippocampal fimbria is further increased at 26 weeks of age compared to single hemizygous Plp1 males
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immune system
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• density of T-lymphocytes (CD3+ cells) in the fimbria is further increased at 26 weeks of age compared to single hemizygous Plp1 males
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• microgliosis in the hippocampal fimbria is further increased at 26 weeks of age compared to single hemizygous Plp1 males
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nervous system
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• microgliosis in the hippocampal fimbria is further increased at 26 weeks of age compared to single hemizygous Plp1 males
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• hippocampal fimbria exhibits APP+ axonal spheroids, microgliosis and astrogliosis, and increased density of T-lymphocytes
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• moderate, but significant, astrogliosis in the hippocampal fimbria at 26 weeks of age
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• APP+ axonal spheroids are present in the hippocampal fimbria and corpus callosum at 26 weeks of age at enhanced levels compared to single hemizygous Plp1 males
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gpm6btm1Kan mutation
(0 available);
any
Gpm6b mutation
(5 available)
Plp1tm1Kan mutation
(1 available);
any
Plp1 mutation
(19 available)
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mortality/aging
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• most die by 4 - 5 months of age with none living past 6 months of age
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behavior/neurological
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• unable to remain on a horizontal bar without support at all ages tested
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• hunchback at 2 - 3 months of age
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• fail to grasp objects with the forelimbs
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muscle
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• hindlimb spasticity is seen at 10 days of age
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• at 2 - 3 months of age mice always have spastic hindlimbs
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nervous system
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• apoptotic oligodendrocytes are seen in the CNS
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• pathology is more severe in the white matter than in the gray matter
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• thickness is reduced to 2/3 that of controls
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• thickness is reduced to 2/3 that of controls
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• reactive microgliosis accompanies neurodegeneration
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• accompanies neurodegeneration
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• processes are longer and thicker and are often seen engulfing axons with a noncompacted cellular process
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• absence of proteolipids, decrease in cholesterol content
• intraperiod lines are partly condensed
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• pathology is more severe in the white matter than in the gray matter
• degeneration is also seen in the retina and the PNS
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• axonal swellings are seen earlier and more frequently than in Plp single null mice
• axonal degeneration in the optic nerve at 4.5 months of age
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• at P14 the optic nerve lacks myelin and at 1 month of age myelination of the optic nerve and spinal cord are clearly delayed
• myelination in the striatal white matter and in spinal cord gray matter is 86% and 67% that of controls
• however, most large caliber axons are myelinated
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vision/eye
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• no reproducible responses are detected at 19 - 25 weeks of age
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hearing/vestibular/ear
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N |
• distortion product otoacoustic emissions are present and major degeneration of the VIIIth cranial nerve is not seen
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• waves II - V (reflecting CNS function) are significantly delayed in mice at 2.5 months of age
• the delay in waves II - V is less pronounced at 4.5 months of age
• at both 2.5 and 4.5 months of age wave III is most delayed
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• moderate pantonal hearing loss across all frequencies
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cellular
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• apoptotic oligodendrocytes are seen in the CNS
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• apoptotic cells are seen in the CNS, some of which are oligodendrocytes
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hematopoietic system
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• reactive microgliosis accompanies neurodegeneration
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immune system
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• reactive microgliosis accompanies neurodegeneration
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gpm6btm1Kan mutation
(0 available);
any
Gpm6b mutation
(5 available)
Plp1tm1Kan mutation
(1 available);
any
Plp1 mutation
(19 available)
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mortality/aging
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• die at 7 - 12 months of age later than males
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behavior/neurological
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• progressive motor impairments similar to males but milder at 4 - 6 weeks of age
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gpm6btm1Kan mutation
(0 available);
any
Gpm6b mutation
(5 available)
Plp1tm1Kan mutation
(1 available);
any
Plp1 mutation
(19 available)
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mortality/aging
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• die at 7 - 12 months of age later than males
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behavior/neurological
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• progressive motor impairments similar to males but milder at 4 - 6 weeks of age
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Allelic
Composition |
Mbpshi/Mbpshi
Plp1tm1Kan/Y
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Genetic
Background |
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SWV |
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mortality/aging
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N |
• double mutants live for more than 6 months unlike Mbpshi homozygotes that die around 3 months of age
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nervous system
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• when present axon sheaths are thinner than normal, often decompacted, lack major dense lines, and have intraperiod lines that are denser than normal
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• dysmyelination with many naked axons
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behavior/neurological
nervous system
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• axonal spheroids are seen unlike in Mbpshi homozygotes
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Plp1tm1Kan mutation
(1 available);
any
Plp1 mutation
(19 available)
|
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nervous system
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• low grade in the hippocampal fimbria
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• mild astrogliosis in the hippocampal fimbria
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• density of axons shows a striking reduction to fewer than half that of controls
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• moderately dysmyelinated due to diminished myelination of axons with the smallest calibers, significant at 40 weeks of age
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behavior/neurological
growth/size/body
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• at 4 and 40 weeks of age
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skeleton
immune system
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• low grade in the hippocampal fimbria
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hematopoietic system
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• low grade in the hippocampal fimbria
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Plp1tm1Kan mutation
(1 available);
any
Plp1 mutation
(19 available)
|
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nervous system
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• hypomyelination with split myelin lamellae
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Allelic
Composition |
Plp1tm1Kan/Y
|
|
Genetic
Background |
involves: 129S1/Sv * 129X1/SvJ |
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Plp1tm1Kan mutation
(1 available);
any
Plp1 mutation
(19 available)
|
|
|
nervous system
|
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• increased numbers of microglia accompany degenerative changes
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• microgliosis in the hippocampal fimbria at 26 weeks of age
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• hippocampal fimbria exhibits APP+ axonal spheroids, microgliosis and astrogliosis
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• mild astrocytosis accompanies degenerative changes
(J:48031)
• moderate, but significant, astrogliosis in the hippocampal fimbria at 26 weeks of age
(J:245100)
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• occasionally inner tongue processes of pligdendrocytes contain degenerated organelles
(J:48031)
• primary glial cultures have increased numbers of oligodendrocytes starting at the second division and persisting through at least the fourteenth division; however no increase in oligodendrocyte proliferation is seen
(J:106182)
• in primary glial cultures oligodendrocyte sheets appear larger, vacuolated, and broken suggesting decreased stability of the myelin sheet
(J:106182)
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• at 6 - 8 weeks, focal axonal swellings containing organelles are seen mostly in areas where small diameter axons predominate throughout the white and gray matter
• by 1 year, numerous large axonal swellings are seen in the optic nerve and spinal cord with some also seen in Purkinje cell axons
• after 1 year, axonal degeneration is seen in the optic nerve and fasciculus gracilis; however, no signs of peripheral neuropathy are seen
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• in areas of axonal swelling the myelin sheath becomes attenuated and is eventually lost though slippage
(J:48031)
• decrease in cholesterol content
(J:193310)
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• APP+ axonal spheroids are present in the hippocampal fimbria and corpus callosum at 26 weeks of age
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• evidence of demyelination is seen at 22 months of age
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behavior/neurological
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• at 16 months of age impaired performance in a rotarod test is seen
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• at 16 months of age impaired performance in a rotarod test is seen
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• older mice develop a slow gait
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hematopoietic system
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• increased numbers of microglia accompany degenerative changes
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• microgliosis in the hippocampal fimbria at 26 weeks of age
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immune system
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• increased numbers of microglia accompany degenerative changes
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• microgliosis in the hippocampal fimbria at 26 weeks of age
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homeostasis/metabolism
Allelic
Composition |
Plp1tm1Kan/Y
|
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Genetic
Background |
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J |
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Plp1tm1Kan mutation
(1 available);
any
Plp1 mutation
(19 available)
|
|
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nervous system
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• myelin is compacted but the distinction between major dense lines and intraperiod lines is less than in wild-type; however, the proportion of myelinated axons, myelin sheath thickness and size range of myelinated fibers are similar to wild-type
• in a few areas double intraperiod lines are seen and myelin sheaths are more susceptible to damage during the fixation process compared to wild-type
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• in mice over 2 months of age, some axonal spheroids
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behavior/neurological
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N |
• no signs of motor dysfunction or impaired coordination are detected
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Allelic
Composition |
Plp1tm1Kan/?
|
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Genetic
Background |
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 |
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Plp1tm1Kan mutation
(1 available);
any
Plp1 mutation
(19 available)
|
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nervous system
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• some attenuated myelin sheaths are seen around swollen axons
• however, in non swollen regions sheaths are of normal thickness
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• at 8 months of age occasional degenerating fibers are seen in the cervical region of the fasciculus gracilis
• at 18 months of age pronounced axonal degeneration is seen in the cervical segments in the thoracic region but not in the lumbar dorsal columns
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behavior/neurological
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• gait ataxia is seen by 18 months of age
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• weakness particularly of the hind limbs develops by 18 months of age
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Analysis Tools
