Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc2tm1Plob mutation
(0 available);
any
Npc2 mutation
(23 available)
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immune system
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• mice have reduced numbers of Valpha14 natural killer T cells compared to wild-type mice as determined by staining with the CD1d-alphaGalCer tetramer
• the number of CD1d-alphaGalCerhigh CD44intermediate NK cells is reduced to 2% of the levels found in wild-type mice and persists over time
• the number of CD1d-alphaGalCerintermediate CD44high NK cells is reduced to 25% of the levels found in wild-type mice but recovered to wild-type levels by week 12
• however, mice have normal numbers of CD4, CD8 and B cells
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• remaining NK cells fail to produce or induce the production of interferon-gamma with either lipids or 2 ug of alphaGalCer as do wild-type
• however, some NK cell expansion can observed at day 6 after alphaGalCer stimulation
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• thymocytes fail to activate the production of IL-2 from Valpha14-DN32.D3 cells in an in vitro assay and the activation of TCB11 cells is reduced by 50% compared to activation levels produced by wild-type thymocytes
• stimulation of DN23.D3 cells by thymocytes or splenocytes pulsed with alphaGalCer, an NK cell agonist, is reduced compared to stimulation by wild-type thymocytes and splenocytes and processing or presenting of the Galalpha1-2GalCer is abolished
• unlike in wild-type cells, splenocytes only present iGb3 at the highest concentration used to DN32.D3 cells in an in vitro assay
• however, thymocytes can activate non-Valpha14 NK cells and presentation of MHC class II-restricted proteins such as ovalbumin is normal
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cellular
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• fibroblasts, splenocytes and bone marrow derived cells contain larger lysosomal compartments compared to those found in wild-type cells
• however, intracellular trafficking is normal
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hematopoietic system
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• mice have reduced numbers of Valpha14 natural killer T cells compared to wild-type mice as determined by staining with the CD1d-alphaGalCer tetramer
• the number of CD1d-alphaGalCerhigh CD44intermediate NK cells is reduced to 2% of the levels found in wild-type mice and persists over time
• the number of CD1d-alphaGalCerintermediate CD44high NK cells is reduced to 25% of the levels found in wild-type mice but recovered to wild-type levels by week 12
• however, mice have normal numbers of CD4, CD8 and B cells
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• remaining NK cells fail to produce or induce the production of interferon-gamma with either lipids or 2 ug of alphaGalCer as do wild-type
• however, some NK cell expansion can observed at day 6 after alphaGalCer stimulation
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• thymocytes fail to activate the production of IL-2 from Valpha14-DN32.D3 cells in an in vitro assay and the activation of TCB11 cells is reduced by 50% compared to activation levels produced by wild-type thymocytes
• stimulation of DN23.D3 cells by thymocytes or splenocytes pulsed with alphaGalCer, an NK cell agonist, is reduced compared to stimulation by wild-type thymocytes and splenocytes and processing or presenting of the Galalpha1-2GalCer is abolished
• unlike in wild-type cells, splenocytes only present iGb3 at the highest concentration used to DN32.D3 cells in an in vitro assay
• however, thymocytes can activate non-Valpha14 NK cells and presentation of MHC class II-restricted proteins such as ovalbumin is normal
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc2tm1Plob mutation
(0 available);
any
Npc2 mutation
(23 available)
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mortality/aging
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• all mice on a 129S1/Sv genetic background had died by ~90 days of age
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc2tm1Plob mutation
(0 available);
any
Npc2 mutation
(23 available)
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growth/size/body
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• lung weight as a % of total body weight is higher
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respiratory system
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• lungs contain 'nests' of vacuolar filled macrophages and enlarged foamy alveolar macrophages
• accumulation of tubular myelin and surfactant aggregates in large airways and large surfactant aggregates next to type II cells or in the alveolar space
• accumulation of surfactant is seen as tight or loosely packed whirls of phospholipid-like surfactant material in focal areas of the alveolar spaces, and as the most common form, string-like surfactant
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• enlarged polymorphonuclear leukocytes or circulating macrophages filled with vacuolar inclusions are seen within lung capillaries
• capillary endothelial cells containing enlarged vacuoles/multivesicular bodies are seen in lungs
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• lung weight as a % of total body weight is higher
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• alveolar macrophages are enlarged and vacuole-filled, some with concentric multilamellar electron dense surfactant-like materials
• alveolar macrophages are laden with free cholesterol with many large, foamy cells; phospholipid levels are elevated 2-fold and cholesterol levels are elevated 8-fold in alveolar macrophage
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• proteinaceous-like material in the alveolar space
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• alveolar type II cells have many autophagosomes
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• alveolar type II cells exhibit 65% more lamellar bodies than wild-type cells
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• alveolar type II cell lamellar bodies are smaller compared to wild-type mice
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• increase in alveolar septum thickness
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• increase in surfactant phospholipid levels
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hematopoietic system
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• alveolar macrophages are enlarged and vacuole-filled, some with concentric multilamellar electron dense surfactant-like materials
• alveolar macrophages are laden with free cholesterol with many large, foamy cells; phospholipid levels are elevated 2-fold and cholesterol levels are elevated 8-fold in alveolar macrophage
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homeostasis/metabolism
immune system
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• alveolar macrophages are enlarged and vacuole-filled, some with concentric multilamellar electron dense surfactant-like materials
• alveolar macrophages are laden with free cholesterol with many large, foamy cells; phospholipid levels are elevated 2-fold and cholesterol levels are elevated 8-fold in alveolar macrophage
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cardiovascular system
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• enlarged polymorphonuclear leukocytes or circulating macrophages filled with vacuolar inclusions are seen within lung capillaries
• capillary endothelial cells containing enlarged vacuoles/multivesicular bodies are seen in lungs
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc2tm1Plob mutation
(0 available);
any
Npc2 mutation
(23 available)
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Neurodegenerative changes affecting cerebullar Purkinje cells of Npc1m1N/Npc1m1N, Npc2tm1Plob/Npc2tm1Plob, and double homozygous mice for Npc1m1N and Npc2tm1Plob
mortality/aging
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• all mice on a genetic background involving 129S1/Sv, BALB/c, C57BL/6 had died by ~130 days of age
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behavior/neurological
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• continuous tremor first detected at ~55 days of age
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• following onset of tremors
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• following onset of tremors
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growth/size/body
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• mice grew normally until ~55 days of age when they began to lose weight
• later onset and less progressive than in Npc1m1N homozygotes
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homeostasis/metabolism
nervous system
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• similar progressive degeneration of loss as in Npc1m1 homozygotes, but later onset
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liver/biliary system
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• about a 6 fold increase in total cholesterol accumulation in the liver at 28 days of age
• about a 10 fold increase in total cholesterol accumulation in the liver at 50 days of age
• no increase in overall cholesterol levels in the brain, putatively due to compensatory losses due to demyelination, neuronal death, and possible imbalance between neuronal cell bodies and distal axons
• on the cellular level in the brain, unesterified cholesterol was stored in neurons within the neocortex, dentate gyrus, hippocampus, and cerebellum
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc2tm1Plob mutation
(0 available);
any
Npc2 mutation
(23 available)
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mortality/aging
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• all mice on a genetic background involving 129S1/Sv and C57BL/6 had died by ~120 days of age
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hematopoietic system
immune system
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc1m1N mutation
(3 available);
any
Npc1 mutation
(72 available)
Npc2tm1Plob mutation
(0 available);
any
Npc2 mutation
(23 available)
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Neurodegenerative changes affecting cerebullar Purkinje cells of Npc1m1N/Npc1m1N, Npc2tm1Plob/Npc2tm1Plob, and double homozygous mice for Npc1m1N and Npc2tm1Plob
mortality/aging
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• all mice on a genetic background involving 129S1/Sv, BALB/c, C57BL/6 had died by ~130 days of age
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growth/size/body
homeostasis/metabolism
nervous system
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• similar progressive degeneration of loss as in Npc1m1 homozygotes
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liver/biliary system
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• about a 6 fold increase in total cholesterol accumulation in the liver at 28 days of age
• about a 10 fold increase in total cholesterol accumulation in the liver at 50 days of age
• no increase in overall cholesterol levels in the brain, putatively due to compensatory losses due to demyelination, neuronal death, and possible imbalance between neuronal cell bodies and distal axons
• on the cellular level in the brain, unesterified cholesterol was stored in neurons within the neocortex, dentate gyrus, hippocampus, and cerebellum
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Analysis Tools