Phenotypes Associated with This Genotype

Genotype
MGI:5305067

• Allelic Composition: App^tm1Dbo/App^tm1Dbo; Npc1^m1N/Npc1^m1N
• Genetic Background: C.Cg-App^tm1Dbo Npc1^m1N

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

mortality/aging

premature death ( J:172769 )

• mutants start to die at 50 days of age

growth/size/body

weight loss ( J:172769 )

• mutants exhibit severe weight loss, with weight at 3 weeks of age lower than seen in single homozygous App mice, but then increases so that by 12 weeks of age, loss of body weight is similar to single Npc1 homozygotes

nervous system

increased brain cholesterol level ( J:172769 )

• mutants exhibit a greater vesicular accumulation of and wider distribution of cholesterol in the cerebellum, the motor cortex, the hippocampus and dentate gyrus than single Npc1 homozygotes

decreased brain size ( J:172769 )

Purkinje cell degeneration ( J:172769 )

• lower number of surviving Purkinje cells in cerebellar lobes VIII and X

astrocytosis ( J:172769 )

• mutants exhibit a greater increase in astrocytosis and microglia activation than in single Npc1 homozygotes

demyelination ( J:172769 )

• mutants exhibit demyelination in the white matter

behavior/neurological

impaired coordination ( J:172769 )

• mutants exhibit an exacerbated motor coordination deficit than seen in single Npc1 homozygotes

homeostasis/metabolism

increased brain cholesterol level ( J:172769 )

• mutants exhibit a greater vesicular accumulation of and wider distribution of cholesterol in the cerebellum, the motor cortex, the hippocampus and dentate gyrus than single Npc1 homozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:172769
Niemann-Pick disease		DOID:14504		J:172769