Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Galctwi mutation
(1 available);
any
Galc mutation
(46 available)
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mortality/aging
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• Background Sensitivity: lifespan of mutants is 45.5 days; death is result of peripheral and cranial nerve palsy
(J:108359)
• Background Sensitivity: the average lifespan of homozygotes in this study is 37 days
(J:126892)
• median survival is 51 days
(J:170081)
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homeostasis/metabolism
behavior/neurological
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• mutants have poorer righting response compared to wild-type or Ptgds2/Galc double mutants
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• mutants barely stagger with strong intentional tremor
(J:108359)
• Background Sensitivity: mean age of onset 21 days
(J:126892)
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• Background Sensitivity: wobbly gait appears at approximately 28-30 days of age
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• moribund mice develop spastic paresis
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nervous system
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• microglia in mutant brains have increased levels of Ptgds2 protein and have irregular thick processes in the region of demyelination
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• Background Sensitivity: lectin-positive macrophages are found in the cerebellum, pons, and medulla more severely on this genetic background than when outcrossed to CAST/EiJ
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• mutants exhibit an increase in oligodendrocyte progenitor cell (OPC) population compared to wild-type
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• levels of psychosine are increased in the forebrain while levels of free sphingosine are lower compared to wild-type mice
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• dramatically increased concentration of psychosine in the pons/medulla which is not impacted by genetic background
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• there are hypertrophied astrocytes with large soma and thick-branched processes in mutant brains
(J:108359)
• Background Sensitivity: increased GFAP staining astrocytes are found in the cerebellar granular layer and pons
(J:126892)
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• white matter exhibits similar reactive astrocytosis as double Galctwi Csf1op mice
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• oligodendrocyte progenitor cells become hypertrophic and have short and stout processes instead of well branched fine processes as in wild-type mice
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• mutants exhibit a moderate decrease in oligodendrocytes
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• sciatic nerves are swollen and demyelination and myelin debris is found in moribund homozygotes
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• 39 day-old mutant brains exhibit demyelination; demyelination appears to be restricted to the CNS
(J:108359)
• Background Sensitivity: extensive demyelination is found in the cerebellar white matter at the moribund stage on this genetic background
(J:126892)
• myelin degeneration in the white matter, with a preferential loss of myelin in large diameter axons
(J:170081)
• sciatic nerves are severely demyelinated
(J:170081)
• however, development (wrapping) of myelin from P15 to P30 is not affected
(J:170081)
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hematopoietic system
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• microglia in mutant brains have increased levels of Ptgds2 protein and have irregular thick processes in the region of demyelination
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• enhanced osteoclast activity
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immune system
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• microglia in mutant brains have increased levels of Ptgds2 protein and have irregular thick processes in the region of demyelination
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• enhanced osteoclast activity
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growth/size/body
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• body weight is reduced starting at P20
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• mutants start to lose weight after P35
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limbs/digits/tail
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• femurs weigh 27% less than wild-type at 32-33 days of age
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skeleton
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• femurs weigh 27% less than wild-type at 32-33 days of age
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• metaphyseal region of femurs show structural differences, with reduced trabecular bone mainly in the secondary spongiosa
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• mice exhibit features of osteopenia
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• decrease in cortical bone thickness in femurs
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• decrease in the number of trabeculae in femurs
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• growth of long bones is retarded
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• reduction of bone deposition in the metaphyseal and epiphyseal region of femurs, but no differences in mineral apposition rate
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• enhanced osteoclast activity
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muscle
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• mutants develop fine twitching in the neck around P20
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cellular
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• mutants exhibit an increase in oligodendrocyte progenitor cell (OPC) population compared to wild-type
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Allelic
Composition |
Galctwi/Galctwi
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Genetic
Background |
involves: 129P2/OlaHsd * C57BL/6J * CE/J |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Galctwi mutation
(1 available);
any
Galc mutation
(46 available)
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mortality/aging
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• Background Sensitivity: average lifespan 48 days of age with nearly all dead before 58 days of age
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Allelic
Composition |
Galctwi/Galctwi
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Genetic
Background |
involves: C57BL/6J * CAST/EiJ * CE/J |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Galctwi mutation
(1 available);
any
Galc mutation
(46 available)
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mortality/aging
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• Background Sensitivity: average lifespan is 61.4 days on this mixed genetic background, longer than on the congenic C57BL/6J background, and there is much wider variation in the life span of individuals, which ranges from 45 to 77 days
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behavior/neurological
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• Background Sensitivity: mean age of tremor onset is 24 days which is delayed when compared with homozygotes on a congenic C57BL/6J background, which have a mean age of onset of 21 days
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• Background Sensitivity: wobbly gait does not develop until 30 days of age or beyond which is delayed compared with the congenic C57BL/6J background on which a wobbly gait appears at approximately 28-30 days of age
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• Background Sensitivity: the longer lived homozygotes display more severe wasting of the hindlimbs when at moribund conditions than do those on a C57BL/6J congenic background
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nervous system
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• lectin-positive macrophages are found in the cerebellum, pons, and medulla in the moribund stage, although to a lesser degree than in homozygotes on a C57BL/6J congenic background
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• on both this mixed genetic background and on the congenic C57BL/6J background the concentration of psychosine in the pons/medulla is dramatically higher than normal and the level of increase is not impacted by genetic background
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• Background Sensitivity: increased GFAP staining astrocytes are found in the cerebellar granular layer to a greater degree on this mixed genetic background than homozygotes on the congenic C57BL/6J background, and increased GFAP staining of astrocytes is found in the pons but to a lesser degree on this mixed genetic background than in homozygotes on the congenic C57BL/6J background
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• Background Sensitivity: sciatic nerves from longer-lived homozygotes on this mixed genetic background show a greater degree of swelling than those on the congenic C57BL/6J background, loss of discrete fasicules, increased cellularity of lipid-filled cells, and demyelination
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• Background Sensitivity: found in the axonal plexus of the granular layer and the cerebellar white matter, but generally not seen in the moribund homozygotes on the C57BL/6J congenic background which die at an earlier age
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• Background Sensitivity: focal areas of demyelination are found in the cerebellar white matter at the moribund stage, but this is less severe than the extensive demyelination of the cerebellar white matter found in homozygotes on a C57BL/6J congenic background at the moribund stage
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Allelic
Composition |
Galctwi/Galctwi
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Genetic
Background |
involves: C57BL/6J * CE/J |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Galctwi mutation
(1 available);
any
Galc mutation
(46 available)
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mortality/aging
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• affected mice live only about 3 months
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behavior/neurological
growth/size/body
hematopoietic system
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• multinucleated macrophages contain a variety of abnormal inclusions
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immune system
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• multinucleated macrophages contain a variety of abnormal inclusions
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muscle
nervous system
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• degeneration in both central and peripheral nervous systems
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Galctwi mutation
(1 available);
any
Galc mutation
(46 available)
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behavior/neurological
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• clinically evident between 15 and 20 days of age, beginning as a fine tremor
• involves the whole body
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• particularly the hindlimbs
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• evident by terminal stages of the disease
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immune system
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• mice show greater macrophage infiltration than Psaptm1Suz mice
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nervous system
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• demonstrated by light and electron microscopic investigations
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• at 15 days of age the only difference found in the cerebral cortex and corpus callosum is rare cells with focal swelling of the cell soma, but by 20 days of age the oligodendrocytes, identified as expressing glutathione S-transferase pi, display irregular, often polygonal swelling of the cell soma, with or without unstained vacuoles, and with thicker processes and some focal swelling, and after 25 days of age the oligodendrocyte cellular processes and soma become progressively shrunken with only markedly shrunken soma, which lack identifiable processes
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• there is gradual decrease in oligodendrocyte number after 35 days of age and very few remain in the cortical layers at 45 days of age
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• demonstrated by light and electron microscopic investigations
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• some degeneration is evident by light and electron microscopic investigations
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• both motor and sensory nerves are involved
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• this mutation is the first spontaneous model for endoneurial edema and increased endoneurial fluid pressure
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• at 40 days of age 10% of oligodendrocytes stain TUNEL positive and there is a correspondence between TUNEL staining and stage of demyelination with the oligodendrocytes with cytoplasmic swelling or thick cellular processes still negative for TUNEL stain and oligodendrocytes with thin or shrunken processes and relatively small soma positive for TUNEL stain
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• mice show greater macrophage infiltration than Psaptm1Suz mice
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• mice show more severe demyelination than do homozygous Psaptm1Suz mice
(J:78223)
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growth/size/body
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• mutant mice are smaller than normal siblings especially noticeable between 15 and 20 days of age
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cellular
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• at 40 days of age 10% of oligodendrocytes stain TUNEL positive and there is a correspondence between TUNEL staining and stage of demyelination with the oligodendrocytes with cytoplasmic swelling or thick cellular processes still negative for TUNEL stain and oligodendrocytes with thin or shrunken processes and relatively small soma positive for TUNEL stain
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homeostasis/metabolism
renal/urinary system
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N |
• light microscopy reveals no abnormalities in kidneys of 5 to 45 day old homozygous mice
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• light microscopy reveals no abnormalities in kidneys of 5 to 45 day old homozygous mice
• ultrastructural analysis shows increasing amounts of epithelial cell inclusions as mutant mice age
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• cytoplasmic inclusions are found in the thin limbs of the loop of Henle in developing papillae of 5 day old mice
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• ultrastructural analysis reveals an increasing amount of cytoplasmic inclusions as mice age
• inclusions are restricted to the thin limbs of the loop of Henle but occasionally are seen in the lumen of thta structure
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• demonstrated by the occurrence of cytoplsmic inclusions in kidney tissue
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Galctwi mutation
(1 available);
any
Galc mutation
(46 available)
Galctwi-3J mutation
(0 available);
any
Galc mutation
(46 available)
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behavior/neurological
growth/size/body
mortality/aging
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• lifespan of mutants is 46.2 days
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behavior/neurological
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• milder than in Galctwi single mutants
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nervous system
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• astrocyte processes are much thinner than in Galctwi single mutants
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Galctwi mutation
(1 available);
any
Galc mutation
(46 available)
Hpgdstm1Urad mutation
(0 available);
any
Hpgds mutation
(13 available)
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mortality/aging
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• lifespan of mutants is 47.3 days
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cellular
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• fewer apoptotic oligodendrocytes are detected in double mutants compared to Galctwi single mutants
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behavior/neurological
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• milder than in Galctwi single mutants
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nervous system
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• astrocyte processes are much thinner than in Galctwi single mutants
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mortality/aging
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• average lifespan is 74.3 days with some surviving up to 94 days, a significant extension of longevity compared with mice homozygous for twitcher only
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hematopoietic system
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• macrophage infiltration in the lymph follicles of the spleen at 94 days of age
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immune system
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• macrophage infiltration in the lymph follicles of the spleen at 94 days of age
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liver/biliary system
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• at 94 days of age macrophage-filled sinusoids compress the hapatocytes and the hepatic architecture is disrupted
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renal/urinary system
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• finely vacuolated cells, which stain PAS-negative, are found within the Bowman capsule in the glomeruli
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• renal tubular epithelium is diffusely vacuolated
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nervous system
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• unlike mice homozygous for only the twitcher mutation, the central nervous system shows normal myelination with rare infiltration of globoid cells at 35-40 days of age but progressively more common at 77 and 94 days of age and the sciatic nerve pathology at 94 days of age is similar to that of 35 to 40 day old twitcher controls
• although the central nervous system maintains myelination, the peripheral nervous system shows distinct demyelination
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homeostasis/metabolism
growth/size/body
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• macrophage infiltration in the lymph follicles of the spleen at 94 days of age
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mortality/aging
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• average lifespan is 37.7 days and nearly all die before 46 days of age
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behavior/neurological
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• between 30 and 35 days of age mice are extremely hyper-responsive in response to touching the cage or lifting the lid
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• between 30 and 35 days of age the hyper-reactivity can include generalized seizures
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nervous system
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• between 30 and 35 days of age the hyper-reactivity can include generalized seizures
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• at 27 days of age many dying neurons with deeply eosinophilic cytoplasm and pyknotic nuclei are present diffusely in the cerebral cortex where activated astrocytes and microglia/macrophages are found
• neuronal degeneration of the hippocampus is most pronounced in CA3 and the subiculum and scattered necrotic cells are also found in the hypothalamus, amygdala, caudate/putamen and lateral septal nuclei
• cerebral cortex and to a lesser extent the white matter have activated astrocytes and microglia/macrophages with many dying cells present
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immune system
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N |
• spleen is free of pathology
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liver/biliary system
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N |
• liver is free of pathology
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homeostasis/metabolism
behavior/neurological
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• the average onset of twitching is earlier in double homozygotes than mice homozygous only for twitcher (22.2 days of age versus 25.9 days of age respectively), although lifespan, body weight and frequency of twitching do not differ significantly
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nervous system
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• leakage of the blood-brain barrier is detected in the cerebrum, hindbrain, and cervical spinal cord as detected by horseradish peroxidase tail vein injection, and immunoglobulin and albumin immunohistochemistry
• lipopolysaccharide injection greatly enhances the blood-brain barrier disruption leading to death
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• the deep cerebellar white matter shows a significant increase in periodic acid-Schiff staining cells and a trend toward increased lectin-positive cells relative to mice homozygous only for twitcher
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• more exaggerated gliosis is found around some vessels and pial surfaces in the double mutants than in mice homozygous only for twitcher
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cardiovascular system
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• leakage of the blood-brain barrier is detected in the cerebrum, hindbrain, and cervical spinal cord as detected by horseradish peroxidase tail vein injection, and immunoglobulin and albumin immunohistochemistry
• lipopolysaccharide injection greatly enhances the blood-brain barrier disruption leading to death
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homeostasis/metabolism
immune system
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• hindbrain has TNF levels elevated above that found in mice homozygous only for twitcher and mice homozygous only for twitcher have significantly elevated TNF levels in hindbrain
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Allelic
Composition |
Galctwi/Galctwi
Il6+/?
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Genetic
Background |
involves: 129S2/SvPas * C57BL/6J * CE/J |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Galctwi mutation
(1 available);
any
Galc mutation
(46 available)
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mortality/aging
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• Background Sensitivity: average lifespan is 39.29 days
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cardiovascular system
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• modest disruption of the blood-brain barrier detected by immunohistochemical detection of IgG or albumin
• lipopolysaccharide injection results in increased blood-brain barrier disruption and further shortens lifespan
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homeostasis/metabolism
immune system
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• hindbrain has elevated TNF levels (9.38 pg/mg versus 6.54 pg/mg)
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nervous system
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• modest disruption of the blood-brain barrier detected by immunohistochemical detection of IgG or albumin
• lipopolysaccharide injection results in increased blood-brain barrier disruption and further shortens lifespan
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• the deep cerebellar white matter has periodic acid-Schiff staining globoid cells and lectin-positive macrophages
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• severe gliosis in both gray and white matter regions
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• most severe in the hindbrain/cervical spinal cord
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behavior/neurological
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• the average onset of twitching is 25.85 days
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mortality/aging
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• mutants have a shorter lifespan than single homozygous Galctwi mice, with a more exacerbated neurological phenotype
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behavior/neurological
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• mutants develop fine twitching in the neck around P18, 2-3 days earlier than Galctwi mice, and shortly after develop a coarse tremor that gradually spreads from the neck to the trunk
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• moribund mice are paralyzed in the hindlimbs
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craniofacial
growth/size/body
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• smaller than either single mutant
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• mutants start to lose weight between P29 and P33
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immune system
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• macrophage infiltration in the CNS white matter observed in Galctwi mice is almost completely blocked: although degenerated myelin is observed in the white matter parenchyma, PAS stain is rarely seen, indicating that PAS+ macrophages, or globoid cells are not observed in demyelinated lesions and that there is an absence of myelin phagocytosis by macrophages
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nervous system
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• white matter exhibits similar reactive astrocytosis as single Galctwi mice, however double mutants have a smaller oligodendrocyte progenitor cell (OPC) population
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• levels of psychosine are increased in the forebrain compared to wild-type mice, however levels are lower than in single Galctwi mice, indicating that levels of psychosine do not correlate with the severity of disease
• mutants have lower levels of free sphingosine compared to wild-type mice, and levels are lower in double mutants than in single Galctwi mice
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• oligodendrocyte progenitor cells become hypertrophic and have short and stout processes instead of well branched fine processes as in wild-type mice
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• mutants exhibit fewer oligodendrocytes than wild-type or single Galctwi mice
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• recruitment of oligodendrocyte progenitor cells in response to demyelination is compromised
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• mutants exhibit a more severe demyelinating pathology than single homozygous Galctwi mice due to inhibition of remyelination and a delay in myelin development, rather than enhanced demyelination
• myelin degeneration is seen in the white matter, with significantly more nonmyelinated axons at P45 in mutants than single Galctwi mice and a preferential loss of myelin in large diameter axons
• sciatic nerves are severely demyelinated
• however, development (wrapping) of myelin from P15 to P30 is not affected
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skeleton
cellular
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• white matter exhibits similar reactive astrocytosis as single Galctwi mice, however double mutants have a smaller oligodendrocyte progenitor cell (OPC) population
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• macrophage infiltration in the CNS white matter observed in Galctwi mice is almost completely blocked: although degenerated myelin is observed in the white matter parenchyma, PAS stain is rarely seen, indicating that PAS+ macrophages, or globoid cells are not observed in demyelinated lesions and that there is an absence of myelin phagocytosis by macrophages
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hematopoietic system
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• macrophage infiltration in the CNS white matter observed in Galctwi mice is almost completely blocked: although degenerated myelin is observed in the white matter parenchyma, PAS stain is rarely seen, indicating that PAS+ macrophages, or globoid cells are not observed in demyelinated lesions and that there is an absence of myelin phagocytosis by macrophages
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