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Phenotypes Associated with This Genotype
Genotype
MGI:3759831
Allelic
Composition
Npc2tm1Plob/Npc2tm1Plob
Genetic
Background
C.129S1-Npc2tm1Plob
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc2tm1Plob mutation (0 available); any Npc2 mutation (23 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• 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
• 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
• 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

cellular
• fibroblasts, splenocytes and bone marrow derived cells contain larger lysosomal compartments compared to those found in wild-type cells
• however, intracellular trafficking is normal

hematopoietic system
• 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
• 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
• 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


Contributing Projects:
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
05/07/2024
MGI 6.23
The Jackson Laboratory