All Phenotypes Npc1<tm1.1Apl> MGI Mouse

Phenotypes associated with this allele

Allelic Composition	Npc1^tm1.1Apl/Npc1^tm1.2Apl Tg(Pcp2-cre)2Mpin/0
Genetic Background	B6.Cg-Npc1^tm1.1Apl/Npc1^tm1.2Apl Tg(Pcp2-cre)2Mpin

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc1^tm1.1Apl mutation (0 available); any Npc1 mutation (74 available)
Npc1^tm1.2Apl mutation (0 available); any Npc1 mutation (74 available)
Tg(Pcp2-cre)2Mpin mutation (1 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

mortality/aging ( J:157113 )

N	• mice do not exhibit premature death

nervous system

nervous system phenotype ( J:157113 )

N	• Purkinje cells exhibit normal electrophysiology

microgliosis ( J:157113 )

Purkinje cell degeneration ( J:157113 )

• 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

tremors ( J:157113 )

• by 13 weeks

ataxia ( J:157113 )

impaired coordination ( J:157113 )

• 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

increased cholesterol level ( J:157113 )

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

growth/size/body

growth/size/body region phenotype ( J:157113 )

N	• mice do not exhibit weight loss

immune system

microgliosis ( J:157113 )

hematopoietic system

microgliosis ( J:157113 )

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:176888 )

• average lifespan is 109 days post tamoxifen injection

nervous system

microgliosis ( J:176888 )

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

increased brain cholesterol level ( J:176888 )

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

Purkinje cell degeneration ( J:176888 )

• 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

astrocytosis ( J:176888 )

• widespread astrocytosis in the cerebellum of tamoxifen-treated mice at 18 weeks of age

abnormal axon morphology ( J:176888 )

• tamoxifen-treated mice exhibit swollen axons in the cortex at 22 weeks of age

axonal spheroids ( J:176888 )

• widespread axonal spheroids in the cerebellum of tamoxifen-treated mice at 18 weeks of age

demyelination ( J:176888 )

• 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

impaired balance ( J:176888 )

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

growth/size/body

weight loss ( J:176888 )

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

hematopoietic system

microgliosis ( J:176888 )

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

homeostasis/metabolism

increased brain cholesterol level ( J:176888 )

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

immune system

microgliosis ( J:176888 )

• 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

Allelic Composition	Npc1^m1N/Npc1^tm1.1Apl Tg(GFAP-cre/ERT2)13Kdmc/0
Genetic Background	B6J.Cg-Npc1^m1N/Npc1^tm1.1Apl Tg(GFAP-cre/ERT2)13Kdmc

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc1^m1N mutation (3 available); any Npc1 mutation (74 available)
Npc1^tm1.1Apl mutation (0 available); any Npc1 mutation (74 available)
Tg(GFAP-cre/ERT2)13Kdmc mutation (1 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

normal phenotype

no abnormal phenotype detected ( J:176888 )

• 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

Allelic Composition	Npc1^m1N/Npc1^tm1.1Apl Tg(Syn1-cre)671Jxm/0
Genetic Background	B6J.Cg-Npc1^m1N/Npc1^tm1.1Apl Tg(Syn1-cre)671Jxm

Find Mice

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:176888 )

• mice show early death, with an average lifespan of 105 days

nervous system

microgliosis ( J:176888 )

• mice show activated microglia in many brain regions

increased brain cholesterol level ( J:176888 )

astrocytosis ( J:176888 )

• mice show activated astrocytes in many brain regions

abnormal axon morphology ( J:176888 )

• mice show severe axonal pathology

axonal spheroids ( J:176888 )

• mice exhibit frequent axonal spheroids in the brainstem

demyelination ( J:176888 )

• mice show loss of myelinated fibers in the corpus callosum

behavior/neurological

impaired balance ( J:176888 )

• mice develop motor deficits in the balance beam

impaired coordination ( J:176888 )

• mice develop motor deficits in the rotarod

growth/size/body

weight loss ( J:176888 )

• mice exhibit progressive weight loss

hematopoietic system

microgliosis ( J:176888 )

• mice show activated microglia in many brain regions

homeostasis/metabolism

increased brain cholesterol level ( J:176888 )

immune system

microgliosis ( J:176888 )

• mice show activated microglia in many brain regions

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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