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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Npc1tm1.1Apl
targeted mutation 1.1, Andrew P Lieberman
MGI:4431252
Summary 4 genotypes


Genotype
MGI:4436742
cn1
Allelic
Composition
Npc1tm1.1Apl/Npc1tm1.2Apl
Tg(Pcp2-cre)2Mpin/0
Genetic
Background
B6.Cg-Npc1tm1.1Apl/Npc1tm1.2Apl Tg(Pcp2-cre)2Mpin
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc1tm1.1Apl mutation (0 available); any Npc1 mutation (72 available)
Npc1tm1.2Apl mutation (0 available); any Npc1 mutation (72 available)
Tg(Pcp2-cre)2Mpin mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
N
• mice do not exhibit premature death

nervous system
N
• Purkinje cells exhibit normal electrophysiology
• as early as 5.5 to 7 weeks, mice exhibit loss of Purkinje cells unlike wild-type mice
• by 10 weeks, mice exhibit a 15% loss of Purkinje cells in lobule X compared with wild-type mice
• however, no further loss of Purkinje cells in lobule X occur between 10 and 20 weeks
• Purkinje cell loss in lobules II-V is greater than 75% at 10 weeks and approaches 100% by 15 weeks

behavior/neurological
• by 13 weeks
• by 10 weeks, mice exhibit difficulties traversing a balance beam unlike wild-type mice
• by 15 weeks, mice exhibit impaired performance on a rotarod compared with wild-type mice
• motor defects are age-dependent

homeostasis/metabolism
• mice exhibit age-dependent unesterified cholesterol accumulation in Purkinje cells unlike in wild-type mice

growth/size/body
N
• mice do not exhibit weight loss

immune system

hematopoietic system




Genotype
MGI:5925342
cn2
Allelic
Composition
Npc1m1N/Npc1tm1.1Apl
Tg(CAG-cre/Esr1*)5Amc/0
Genetic
Background
B6J.Cg-Npc1m1N/Npc1tm1.1Apl Tg(CAG-cre/Esr1*)5Amc
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc1m1N mutation (3 available); any Npc1 mutation (72 available)
Npc1tm1.1Apl mutation (0 available); any Npc1 mutation (72 available)
Tg(CAG-cre/Esr1*)5Amc mutation (9 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• average lifespan is 109 days post tamoxifen injection

nervous system
• widespread microgliosis in the cerebellum of tamoxifen-treated mice at 18 weeks of age
• accumulation of unesterified cholesterol in cerebellar lobule X in tamoxifen-treated mice at 18 weeks of age
• progressive anterior-to-posterior Purkinje cell loss in tamoxifen-treated mice
• cells in anterior lobules degenerate early and those in posterior lobules are more resistant to degeneration
• widespread astrocytosis in the cerebellum of tamoxifen-treated mice at 18 weeks of age
• tamoxifen-treated mice exhibit swollen axons in the cortex at 22 weeks of age
• widespread axonal spheroids in the cerebellum of tamoxifen-treated mice at 18 weeks of age
• tamoxifen-treated mice exhibit demyelination in the corpus callosum at 22 weeks of age
• widespread secondary demyelination in the cerebellum of tamoxifen-treated mice at 18 weeks of age

behavior/neurological
• mice injected with tamoxifen at 6 weeks of age exhibit impaired balance beam performance by 12 weeks which progresses with age

growth/size/body
• mice injected with tamoxifen at 6 weeks of age start to lose weight around 16 weeks of age

hematopoietic system
• widespread microgliosis in the cerebellum of tamoxifen-treated mice at 18 weeks of age

homeostasis/metabolism
• accumulation of unesterified cholesterol in cerebellar lobule X in tamoxifen-treated mice at 18 weeks of age

immune system
• widespread microgliosis in the cerebellum of tamoxifen-treated mice at 18 weeks of age

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Niemann-Pick disease DOID:14504 J:176888




Genotype
MGI:5925344
cn3
Allelic
Composition
Npc1m1N/Npc1tm1.1Apl
Tg(GFAP-cre/ERT2)13Kdmc/0
Genetic
Background
B6J.Cg-Npc1m1N/Npc1tm1.1Apl Tg(GFAP-cre/ERT2)13Kdmc
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc1m1N mutation (3 available); any Npc1 mutation (72 available)
Npc1tm1.1Apl mutation (0 available); any Npc1 mutation (72 available)
Tg(GFAP-cre/ERT2)13Kdmc mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype
• mice treated with tamoxifen at 6 weeks of age exhibit normal weight gain, motor performance, and survival and do not show Purkinje cell loss, axonal spheroids, demyelination, or activated astrocytes or microglia in the cerebellum, and no functional alterations in synaptic transmission




Genotype
MGI:5925346
cn4
Allelic
Composition
Npc1m1N/Npc1tm1.1Apl
Tg(Syn1-cre)671Jxm/0
Genetic
Background
B6J.Cg-Npc1m1N/Npc1tm1.1Apl Tg(Syn1-cre)671Jxm
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc1m1N mutation (3 available); any Npc1 mutation (72 available)
Npc1tm1.1Apl mutation (0 available); any Npc1 mutation (72 available)
Tg(Syn1-cre)671Jxm mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice show early death, with an average lifespan of 105 days

nervous system
• mice show activated microglia in many brain regions
• mice show activated astrocytes in many brain regions
• mice show severe axonal pathology
• mice exhibit frequent axonal spheroids in the brainstem
• mice show loss of myelinated fibers in the corpus callosum

behavior/neurological
• mice develop motor deficits in the balance beam
• mice develop motor deficits in the rotarod

growth/size/body
• mice exhibit progressive weight loss

hematopoietic system
• mice show activated microglia in many brain regions

homeostasis/metabolism

immune system
• mice show activated microglia in many brain regions





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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
03/12/2024
MGI 6.23
The Jackson Laboratory