Phenotypes associated with this allele

• Allele Symbol: Npc1^tm1Tacf
• Allele Name: targeted mutation 1, The Addi and Cassi Fund
• Allele ID: MGI:6315233
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Npc1^tm1Tacf/Npc1^tm1Tacf	B6(Cg)-Npc1^tm1Tacf	MGI:6359477
ht2	Npc1^tm1Tacf/Npc1^tm2Tacf	B6(Cg)-Npc1^tm1Tacf Npc1^tm2Tacf	MGI:6359481

Genotype
MGI:6359477

hm1

• Allelic Composition: Npc1^tm1Tacf/Npc1^tm1Tacf
• Genetic Background: B6(Cg)-Npc1^tm1Tacf

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

behavior/neurological

abnormal object recognition memory ( J:266795 )

• in the test session of the novel object recognition test, 8 week old, but not 5 week old, mice show impaired memory recognition

impaired learning ( J:266795 )

• mice are unable to learn on repeated testing of an increasingly difficult motor task on the rotarod

decreased anxiety-related response ( J:266795 )

• in the elevated plus maze, mice spend more time in the open arms and enter the open arms more often, indicating decreased anxiety

abnormal response to novel object ( J:266795 )

• mice show reduced exploratory behavior in the familiarization session of the novel object recognition test in 8 week old mice but no differences in exploration were seen in the test sessions

tremors ( J:266795 )

• at approximately 7 weeks of age, mice show onset of visible tremors

ataxia ( J:266795 )

• at approximately 7 weeks of age, mice show onset of visible ataxia

impaired coordination ( J:266795 )

• mice show impaired coordination at 7 weeks of age

• mice are unable to stand or walk on the rod in both the learning and acceleration sessions, with lower time of latency to fall

increased grip strength ( J:266795 )

• forelimb grip strength increases with age, being higher in 8 week old mice than in wild-type mice

abnormal gait ( J:266795 )

• mice show reduced hind paw angles

• however, no differences in the number of steps, or the stride or step length are seen

increased locomotor activity ( J:266795 )

• mice travel longer distance at 8 weeks than at 5 weeks, indicating an age-associated increased in activity

• hyperactivity is seen during the active (dark) phase of the circadian cycle which increases with age

hypoalgesia ( J:266795 )

• mice have a slightly higher pain threshold, presenting a longer delay before licking their front paws

cardiovascular system

dilated liver sinusoidal space ( J:266795 )

• liver shows sinusoid swelling

growth/size/body

decreased body weight ( J:266795 )

• decrease in weight at 8 weeks of age

slow postnatal weight gain ( J:266795 )

• mice show normal weight at 4 weeks of age but reduced weight gain until 7 weeks and a decrease in weight at week 8

homeostasis/metabolism

increased liver cholesterol level ( J:266795 )

• mice show accumulation of free and total cholesterol in the liver

increased ceramide level ( J:266795 )

• mice show an accumulation of dihydroceramide, lactosylceramide and gangliosides, particularly GM2 and GM3, and reduced monohexosylceramide levels and a slight increase in ceramide levels in the brain

liver/biliary system

abnormal liver morphology ( J:266795 )

• accumulation of lipids in vacuole-like inclusions in the liver

• macrophage infiltration is seen in the liver

• liver shows a different organization of hepatocytes

dilated liver sinusoidal space ( J:266795 )

• liver shows sinusoid swelling

increased liver cholesterol level ( J:266795 )

• mice show accumulation of free and total cholesterol in the liver

mortality/aging

premature death ( J:266795 )

• mice have a shorter lifespan with an average of 9 weeks

prenatal lethality, incomplete penetrance ( J:266795 )

• 18% birthrate

nervous system

abnormal Purkinje cell morphology ( J:266795 )

• Purkinje cells show a soma reduction together with alterations in the dendritic pattern

abnormal Purkinje cell dendrite morphology ( J:266795 )

• Purkinje cells show a soma reduction together with alterations in the dendritic pattern

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Niemann-Pick disease type C1		DOID:0070113	OMIM:257220	J:266795

Genotype
MGI:6359481

ht2

• Allelic Composition: Npc1^tm1Tacf/Npc1^tm2Tacf
• Genetic Background: B6(Cg)-Npc1^tm1Tacf Npc1^tm2Tacf

behavior/neurological

impaired learning ( J:266795 )

• mice are unable to learn on repeated testing of an increasingly difficult motor task on the rotarod

decreased anxiety-related response ( J:266795 )

• in the elevated plus maze, mice spend more time in the open arms and enter the open arms more often, indicating decreased anxiety

tremors ( J:266795 )

• at approximately 7 weeks of age, mice show onset of visible tremors

ataxia ( J:266795 )

• at approximately 7 weeks of age, mice show onset of visible ataxia

impaired coordination ( J:266795 )

• mice show impaired coordination at 7 weeks of age

• mice are unable to stand or walk on the rod in both the learning and acceleration sessions, with lower time of latency to fall

abnormal gait ( J:266795 )

• mice show reduced hind paw angles

• however, no differences in the number of steps, or the stride or step length are seen

increased locomotor activity ( J:266795 )

• mice travel longer distance at 8 weeks than at 5 weeks, indicating an age-associated increased in activity

• hyperactivity is seen during the active (dark) phase of the circadian cycle which increases with age

abnormal pain threshold ( J:266795 )

• mice have a slightly higher pain threshold, presenting a longer delay before licking their front paws but a reduced latency to jumping suggesting higher sensitivity to pain in the hind paws

growth/size/body

decreased body weight ( J:266795 )

• decrease in weight at 8 weeks of age

slow postnatal weight gain ( J:266795 )

• mice show normal weight at 4 weeks of age but reduced weight gain until 7 weeks and a decrease in weight at week 8

homeostasis/metabolism

increased liver cholesterol level ( J:266795 )

• mice show accumulation of free and total cholesterol in the liver

increased ceramide level ( J:266795 )

• mice show an accumulation of dihydroceramide, lactosylceramide and gangliosides, particularly GM2 and GM3, and reduced monohexosylceramide levels and a slight increase in ceramide levels in the brain

liver/biliary system

increased liver cholesterol level ( J:266795 )

• mice show accumulation of free and total cholesterol in the liver

mortality/aging

premature death ( J:266795 )

• mice have a shorter lifespan with an average of 9 weeks

prenatal lethality, incomplete penetrance ( J:266795 )

• 22% birth rate

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Niemann-Pick disease type C1		DOID:0070113	OMIM:257220	J:266795