Phenotypes Associated with This Genotype

Genotype
MGI:3698042

• Allelic Composition: Htt^tm5Mem/Htt^tm5Mem
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

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

nervous system

abnormal striatum morphology ( J:60937 , J:111237 )

• the levels of both the endogenous excitotoxin quinolinic acid (QUIN) and its bioprecursor, 3-hydroxykynurenine (3-HK) are increased in the striatum beginning at 15 months of age, similarly to that seen in Huntington disease patients (J:111237)

abnormal medium spiny neuron morphology ( J:60937 )

• exhibit relocation of the mutant protein to the nucleus in medium sized spiny neurons and much later, the formation of morphologic nuclear inclusions (at around 10 months) and insoluble aggregate that are hallmarks of Huntington's Disease in humans

abnormal cerebral cortex morphology ( J:111237 )

• QUIN and 3-HK levels are increased in the cortex beginning at 15 months of age, as seen in patients with Huntington disease

neuronal intranuclear inclusions ( J:60937 )

• observed at 10 months

abnormal nervous system physiology ( J:99425 )

• between 8 and 12 weeks of age, striatal mitochondria develops resistance to calcium, becoming equally sensitive to calcium as cortical mitochondria, whereas in wild-type, striatal mitochondria is more sensitive to calcium than cortical mitochondria

behavior/neurological

abnormal behavior ( J:99425 )

• onset of persistent rubbing and irritability from 12 to 16 months of age

limb grasping ( J:99425 )

• onset of clasping behavior from 12 to 16 months of age

tremors ( J:99425 )

• onset of trembling from 12 to 16 months of age

decreased locomotor activity ( J:99425 )

• onset of hypoactivity from 12 to 16 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:60937 , J:99425 , J:111237