Phenotypes associated with this allele

• Allele Symbol: Htt^tm8Mem
• Allele Name: targeted mutation 8, Marcy E MacDonald
• Allele ID: MGI:3697907
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Htt^tm8Mem/Htt^tm8Mem	involves: 129S1/Sv * 129X1/SvJ	MGI:3698415
ht2	Htt^tm6Mem/Htt^tm8Mem	involves: 129S1/Sv * 129X1/SvJ * Swiss Webster	MGI:3698408

Genotype
MGI:3698415

hm1

• Allelic Composition: Htt^tm8Mem/Htt^tm8Mem
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

mortality/aging

preweaning lethality, complete penetrance ( J:72915 )

• no homozygous pups are observed in litters; time of lethality is not specified

Genotype
MGI:3698408

ht2

• Allelic Composition: Htt^tm6Mem/Htt^tm8Mem
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Swiss Webster

mortality/aging

premature death ( J:72915 )

• some severely affected mutants die within 1 month of weaning

growth/size/body

decreased body size ( J:72915 )

• small throughout postnatal development and adulthood

decreased body weight ( J:72915 )

• mutants weigh significantly less at 1 week after birth and throughout adult life

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:72915 )

• develop a progressive movement disorder, with variable movement abnormalities evident from 2 months of age

limb grasping ( J:72915 )

• first indications of movement abnormalities occur at around 2 months of age when mutants exhibit stiff tail and hindlimb clasping during tail suspension

tremors ( J:72915 )

• resting tremors develop over time

abnormal locomotor coordination ( J:72915 )

• over time, exhibit difficulties walking after handling

abnormal gait ( J:72915 )

• exhibit abnormal patterns of walking, including dragging hind limbs and a hopping gait that lacks normal alternating left-right steps

bradykinesia ( J:72915 )

• at the most advanced stages, most mutants become hypokinetic

paralysis ( J:72915 )

• progressively develop paralysis of the limbs and tail

seizures ( J:72915 )

• seizure-like episodes develop over time

nervous system

nervous system phenotype ( J:72915 )

N • mutants do not exhibit the striatal pathology that is seen in Huntington Disease

seizures ( J:72915 )

• seizure-like episodes develop over time

abnormal brain ventricle morphology ( J:72915 )

• mutants show a range of ventricle sizes, however, ventricle size is not correlated with the progressive movement disease as mutants with normal sized ventricles develop the disease and some asymptomatic mutants have enlarged ventricles

enlarged lateral ventricles ( J:72915 )

• between 2 and 19 months of age, about 50% of mutants have enlarged lateral and third ventricles, extending from the anterior striatum to the level of the hippocampus

enlarged third ventricle ( J:72915 )

• between 2 and 19 months of age, about 50% of mutants have enlarged lateral and third ventricles, extending from the anterior striatum to the level of the hippocampus

homeostasis/metabolism

increased susceptibility to malignant hyperthermia ( J:72915 )

• exhibit increased sensitivity to anesthesia-induced death, tolerating only 50-80% of the dose delivered to controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	Huntington's disease	DOID:12858	OMIM:143100	J:72915