Phenotypes associated with this allele

• Allele Symbol: Htt^tm4Mem
• Allele Name: targeted mutation 4, Marcy E MacDonald
• Allele ID: MGI:1861934
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Htt^tm4Mem/Htt^tm4Mem	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:3698039
ht2	Htt^tm4Mem/Htt^+	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:3698040

Genotype
MGI:3698039

hm1

• Allelic Composition: Htt^tm4Mem/Htt^tm4Mem
• 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: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

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 12-15 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 12-15 months

abnormal nervous system physiology ( J:99425 )

• between 5 and 12 months 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

limb grasping ( J:99425 )

• observe clasping behavior is some mutants by one year 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

Genotype
MGI:3698040

ht2

• Allelic Composition: Htt^tm4Mem/Htt⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

nervous system

abnormal striatum morphology ( J:60937 )

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 and insoluble aggregate that are hallmarks of Huntington's Disease in humans, although at a slower rate than seen in homozygotes

neuronal intranuclear inclusions ( J:60937 )

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