Phenotypes associated with this allele

• Allele Symbol: Npc1^tm2Tacf
• Allele Name: targeted mutation 2, The Addi and Cassi Fund
• Allele ID: MGI:6315236
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Npc1^tm2Tacf/Npc1^tm2Tacf	B6(Cg)-Npc1^tm2Tacf	MGI:6359479
ht2	Npc1^tm1Tacf/Npc1^tm2Tacf	B6(Cg)-Npc1^tm1Tacf Npc1^tm2Tacf	MGI:6359481

Genotype
MGI:6359479

hm1

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

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

mortality/aging

prenatal lethality, incomplete penetrance ( J:266795 )

• very low birth rate, with only 2% of homozygotes born

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