Analysis Tools
nervous system
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• swellings of the inner tongue of myelin
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Allele Symbol Allele Name Allele ID |
Cnptm1(cre)Kan targeted mutation 1, Klaus-Armin Nave MGI:3051635 |
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| Summary |
26 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• swellings of the inner tongue of myelin
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most mutants die between 7 and 11 months
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• obvious gait abnormalities are seen
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• round 4 months impaired hindlimb movement that develops into hindlimb paralysis by about 6 months of age is seen
• mutants between 9 and 15 months of age are unable to balance on a round bar for more than a few seconds
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• around 4 months of age mutants develop convulsions when lifted by the tail
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• weight loss is seen in older mutants
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• mutants between 9 and 15 months of age display muscle weakness
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• around 4 months of age mutants develop convulsions when lifted by the tail
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• reactive astrogliosis is seen in the corpus callosum and to a lesser extent in the spinal cord
• reactive microglia are seen in the corpus callosum and the white matter of the cerebellum and to a lesser extent in the spinal cord
• microglial activation can be seen by 3.5 months of age
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• axonal swellings with attenuated myelin sheaths and axon loss are seen in 7 month old mutants
• white matter tracts and overall brain size are reduced in 7 month old mutants
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• concentration of myo-inositol is increased in the corpus callosi at 8 months of age, indicating gliosis
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• late-onset astrogliosis
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• mice show early-onset progressive axonopathy, with optic nerves showing pathological axonal profiles already at P30 and their number progressively increasing
• mice show a trend toward reduced axon density is seen at P30 and P75 which reaches significance at 12 months of age and leads to axonal loss
• dorsal white matter in spinal cords shows axonopathy in 12-month-old mice
• however, mice show normal axonal diameters in the optic nerves
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• number of myelin whorls (multilamellar structures that display the periodicity of CNS myelin devoid of a discernible axon; i.e. remnants of degenerating myelinated fibers with relative sparing of myelin membranes) is increased in optic nerves of 12-month-old mice, indicating axonal degeneration but not myelin pathology
• however, mice show normal myelin biogenesis and composition and numbers of myelin outfoldings, normal myelin sheath thickness, unchanged inner-tongue inclusions and axoplasmic inclusions, and normal mature oligodendrocytes
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• visually evoked potential amplitudes are reduced indicating that transmission of signals via the optic nerves to the visual cortex is impaired
• however, mice show sizeable visually evoked potentials with normal thresholds and latency, indicating normal speed of action potential propagation
• electroretinography shows normal ERG waveforms, thresholds, and amplitudes of a- and b-waves at 8.5 months of age indicating normal retinal function
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• concentration of myo-inositol is increased in the corpus callosi at 8 months of age, indicating gliosis
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• concentration of myo-inositol is increased in the corpus callosi at 8 months of age, indicating gliosis
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| N |
• mice show no obvious behavioral phenotype
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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N |
• mice exhibit normal developmental myelination
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit very-long-chain fatty acid accumulation in different lipid classes and acylcarnitines
• C26:0 levels are increased 15-fold in brain and 12-fold in spinal cord
• 1-hexacosanoyl-sn-glycero-3-phosophocholine (C26:0-lysoPC) levels are increased 13-fold in the brain, 24-fold in the spinal cord, and 17-fold in the blood
• C26:0-carnitine levels are increased 40-fold in brain, 33-fold in spinal cord, and 16-fold in the blood
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| adrenoleukodystrophy | DOID:10588 |
OMIM:300100 |
J:257393 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• histological abnormalities are similar to those in germline null mice
• decrease in myelin lipid levels in the cerebellum compared to controls at 12 months of age but not at 6 months of age
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• while the overall number of Purkinje cells is similar to controls, regions with smaller sized or absent Purkinje neurons relative to controls are seen
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• decrease in myelin lipid levels in the cerebellum compared to controls at 12 months of age but not at 6 months of age
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• hFA-GalCer galactolipids are absent from the brain at 10 weeks of age
• total loss of brain hFA-galactolipids at 3 months of age
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| N |
• unlike germline null mice, no defects in learning are detected using a water T maze or a morris water maze
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• at 12 months of age
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• at 12 months of age
• reduction in vertical activity is more severe than that in horizontal activity
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• decrease in spontaneous activity at 12 months of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• double mutants die between P12 and P14
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• double mutants develop hindlimb weakness around P8-10
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• around P8-10 double mutants begin to lose weight
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• from P0 to P14, no oligodendrocytes can be detected in double mutants
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• large clusters of unmyelinated axons that show signs of degeneration and are not surrounded by Schwann cells are seen
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• loss of oligodendrocytes and a subset of Schwann cells results in a dramatic decrease in the number of myelinated fibers in the nerves and large clusters of unmyelinated axons are seen
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die during third postnatal week
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• 2-fold higher levels of apoptotic cells (having blebbed processes, fragmented nuclei) are observed in premyelinating oligodendrocytes compared to controls; transition from premyelinating to mature oligodendrocytes is blocked when assayed at P7
• postmitotic oligodendrocytes are generated but then undergo apoptosis
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• severe loss of myelin is observed in spinal cord at P16, but spinal roots are myelinated
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• severe loss of myelination in CNS white matter tracts is observed at P16
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• about one-third of mutant mice died between 20 and 30 days
• mutants that survived past 1 month of age rarely died prematurely
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| N |
• homozygous mutant mice that are heterozygous for Cnp1tm1(cre)Kan, in which cre mediated recombination is induced in oligodendrocyte and Schwann cells, were normal at birth
• did not reveal any obvious oligodendrocytes loss, or apoptosis
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• severe dysmyelination of the spinal white matter which was almost of devoid of myelin at P20
• the corpus callosum and the cerebellar white matter also showed a marked reduction of myelin
• but no obvious ultrastructural defects in the myelin architecture was found
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• the motor performance on rotarod testing was markedly lower
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• impaired control of hindlimb movements starting at 2 weeks of age
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• mutant mice lagged behind controls in weight gain
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• overall breeding performance was poor
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• develop to term but die in the second post natal week
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| N |
• central nervous system myelination is normal up to 11 days of age (optic nerve and corpus callosum)
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• severely defective myelination in the peripheral nervous system
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• double mutants die between P12 and P14
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• double mutants develop hindlimb weakness around P8-10
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• around P8-10 double mutants begin to lose weight
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• from P0 to P14, no oligodendrocytes can be detected in double mutants
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• large clusters of unmyelinated axons that show signs of degeneration and are not surrounded by Schwann cells are seen
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• loss of oligodendrocytes and a subset of Schwann cells results in a dramatic decrease in the number of myelinated fibers in the nerves and large clusters of unmyelinated axons are seen
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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N |
• mice do not exhibit any functional defects in nerves
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• Cajal bands are disrupted
• increased Schmidt-Lanterman incisures at 6 weeks
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• supernumerary
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• myelin outfoldings, focal hypermyelination and onion bulbs with thin myelin
• defects increase with time
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• focal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants develop hyperplasia of the salivary glands later in life
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• mutants develop hyperplasia of the salivary glands later in life
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• increase in white matter volume
• progressive enlargement of all white matter tracts
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• myelinated axons of the corpus callosum that intermingle with glial cells are in disarray
• density of myelinated axons in the ventral corpus callosum is decreased by 36.6% at 3 months of age
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• oligodendroglial hypertrophy is seen at 4 months of age
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• increase in numbers of myelinating and nonmyelinating Schwann cells
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• increase in myelin sheath thickness
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• sciatic nerves are increased in size
• myelinated axons are more loosely spaced in sciatic nerves
• number of myelinated axons in the sciatic nerve is higher at 3 months of age; increase in myelination is primarily for small caliber axons
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• hypermyelination in both white and gray matter
• hypermyelination is primarily a consequence of additional membrane wraps and not by altered ultrastructure
• increase in myelin thickness is seen for axons of all calibers, however not all fibers are visibly hypermyelinated
• however, do not see ectopic myelination of CNS axons that normally are unmyelinated
• normally nonmyelinated C-fiber axons are spirally enwrapped by Remak Schwann cells; up to 10 membrane layers per axon are seen resulting in non compacted myelin
• Remak Schwann cells also ensheath bundles of collagen fibrils
• myelin outfoldings of variable length and aberrant myelin depositions are seen in the corpus callosum
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• poor breeding
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• at 6 months of age, optic nerves show no alterations in myelin sheath thickness, percentage of myelinated axons, or frequency of degenerating/degenerated axons relative to those in controls mice
• no axonopathy, astrogliosis or microgliosis is observed
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• at P75, mice exhibit numerous myelin outfoldings in the CNS (e.g. optic nerve)
• myelin outfoldings do not exhibit a pin-needle-like shape but represent large sheets of compacted multilayered membrane stacks that extend considerably away from the myelinated axon
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• mice display disrupted assembly of septin filaments in CNS myelin
• abundance of all myelin septins (SEPT2, SEPT4, SEPT7,SEPT8) is strongly reduced in myelin purified from mutant brains
• abundance of the membrane phospholipid phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2) is reduced in myelin purified from mutant brains
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• at 6 months of age, nerve conduction velocity in the spinal cord is reduced by 15.5%
• however, no nodal or paranodal abnormalities are observed
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• while the abundance of SEPTIN2 is markedly reduced in sciatic nerve lysates as expected, the abundance of other septin subunits expressed in PNS myelin (SEPTIN7, SEPTIN8, SEPTIN9, and SEPTIN11) is also substantially lower than that in sciatic nerve lysates of control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most mice die by 12 weeks of age
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• in the proximal and distal small intestine at 2 and 7 weeks
• however, the number of enteric neurons in the colon is not significantly different
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• in the proximal and distal small intestine at 2 and 7 weeks
• however, the number of glia in the colon is not significantly different
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• loss of nitrergic inhibitory neuron
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• profound in more proximal regions of the small intestine
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• of enteric neurons in proximal and distal small intestine
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• after 2 weeks of age
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• after 2 weeks of age
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• at about 6 to 8 weeks of age
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• small diameter colon
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• massive dilation within the proximal small bowel with dark-colored luminal content and relative contraction of the distal small bowel with no stool pellets in the colon or rectum
• small diameter small intestine
• however, no stenosis or mechanical cause of the obstruction is evident
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• in enteric neurons and glia
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all homozygotes die before day 16 or 17
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• progressive weight loss from 8 days of age onward
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• size is normal until about 8 days of age
• noticeably smaller in stature by 12 days of age
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• progressive development of neurological disorders by 12 days of age
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• cannot maintain their balance on a stationary beam at 16 days of age
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• severe motor coordination defects at 16 days of age
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• day 16 mice hold their legs to the side and away from the body
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• hypomobility at 16 days of age
• nearly immobile in open field tests
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• potassium channels become mislocated to the paranodal region adjacent to the normally distributed sodium channels
• abnormal association of paranodal loops with axons in the white matter of the spinal cord
• axonal accumulation of mitochondria and smooth endoplasmic reticulum
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• axonal swelling
• axonal degeneration
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• conduction velocity of tibial/plantar nerves is reduced about 50%
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 91% are dead by 12 months of age
• none survive past 13 months
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• hind limb ataxia in about 14% of mice by 3 months of age
• symptoms most obvious after 9 months
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• hind limb paralysis develops eventually
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• hind limb paresis develops over 12 months
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• defects seen in rostral white matter by 4 months of age
• defects in the hippocampal commissure and cerebellar white matter less extensive
• defects become more extensive with time
• subcortical white matter degeneration increases as behavioral disorders progress
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• defective peroxisomes in oligodendrocytes
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• activated microglia and macrophage appear early
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• axonal swelling appears early in the corpus callosum and spinal cord
• gradual loss of myelinated nerve fibers
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• very long chain fatty acids become progressively increased in myelin
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• difficulty breathing develops after 12 months
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• activated microglia and macrophage appear early
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• infiltration of T cells into demyelinated regions of the brain by 4 months
• B cell infiltration sometimes seen as well
• proinflammatory proteins become more abundant
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• activated microglia and macrophage appear early
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• motor coordination defects
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• progressive weight loss after P13
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• the formation of the distinct paranode domain in sciatic nerve fibers or in CNS myelinated fibers is perturbed with Caspr (Cntnap1) protein not remaining localized to the paranodal region and appearing diffused throughout the internode
• shaker-type potassium channels and Caspr2 (Cntnap2) protein are redistributed from the juxtaparanode to the paranodal space
• however, ankrynG and NF186 remain localized to the nodes, similar to controls
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• loss of septae-like junctions, formed between the glial paranodal loops and the axon, is seen in the paranodal regions of the sciatic nerve, spinal cord white matter tracts and in Purkinje axons, with accumulation of organelles in the node
• in the CNS myelinated axons, the paranodal loops are often everted away from the axon, astrocytic processes infiltrate the paranodal space, and the parallel arrays of cytoskeletal neurofilaments are disrupted
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• although the abundance of SEPTIN9 is markedly reduced in sciatic nerve lysates as expected, the abundance and localization of other septin subunits expressed in PNS myelin (SEPTIN2, SEPTIN7, SEPTIN8 and SEPTIN11) are similar to those in sciatic nerve lysates of control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• accumulation of long chain fatty acids in the cerebellum
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| N |
• mice exhibit normal reproduction
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| N |
• mice exhibit normal coordination on a rotarod test at 6 and 12 months
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| N |
• mice exhibit normal growth
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| N |
• mice exhibit normal myelination and cerebellum morphology
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at P14
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• at P14
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• spinal cord axons lack myelination
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• density of T-lymphocytes (CD3+ cells) in the fimbria is increased at 26 weeks of age
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• microgliosis in the hippocampal fimbria at 26 weeks of age
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• density of T-lymphocytes (CD3+ cells) in the fimbria is increased at 26 weeks of age
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• microgliosis in the hippocampal fimbria at 26 weeks of age
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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, 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
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hereditary spastic paraplegia 2 | DOID:0110773 |
OMIM:312920 |
J:245100 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutant Schwann cells display arrested radial growth and reduced longitudinal growth
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• there is a 1.9-fold increase in the number of Schwann cells in mutant nerves compared with controls
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• dramatic reduction in the cross-sectional area of peripheral mutant nerves which is first significant at P7 although these are not significantly different from controls until P21
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• in unmyelinated, large diameter axons, in addition to some vacuolation and redundant basal lamina, the axonal membrane was highly irregular in outline
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• internodes in mutant quadriceps nerves at P21 show a wider range of lengths compared with control nerves and mean values are reduced
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• electron microscopy reveals that myelin is consistently thinner than normal; this aberrant ensheathment persists from P7 until P90; growth of the myelin sheath is retarded and/or arrested
• other derangements, such as myelin outfoldings, were also observed at low frequency in the mutant from P7 onwards but not in controls
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• in P21 sciatic nerve lysates, there is a decrease in the amount of the major peripheral myelin protein P0, suggesting a deficit in myelin production
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• nerve conduction velocities of mutant nerves are severely reduced from 38.7 +/- 0.7 m/s to 11.7 +/- 1.5 m/s
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• poorer performance in the Rotarod test at P42; test was performed at two different speeds, 24 and 32 rpm
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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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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• 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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• 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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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/23/2024 MGI 6.23 |
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