Phenotypes Associated with This Genotype

Genotype
MGI:3800927

• Allelic Composition: Tg(HTT*97Q)IXwy/0
• Genetic Background: FVB-Tg(HTT*97Q)IXwy

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

nervous system

nervous system phenotype ( J:208675 )

N • cerebellar weight does not differ from wild-type

decreased brain weight ( J:137345 )

• at 12 months, forebrain weight (whole brain minus cerebellum and olfactory bulb) is 20% lower than wild-type controls; however cerebellar weight is comparable

abnormal forebrain morphology ( J:157723 )

• mice exhibit decreased forebrain weight loss compared with wild-type mice

decreased forebrain size ( J:208675 )

decreased striatum size ( J:137345 )

• at 12 months, robust decrease in striatal volume (28% of wild-type) is observed

abnormal cerebral cortex morphology ( J:137345 )

• at 12 months, robust decrease in cerebral cortex volume (32% of wild-type) is observed

brain atrophy ( J:137345 )

• at 6 months of age, brains do not display any obvious pathology, but at 12 months, brains are visibly atrophic compared to wild-type

forebrain atrophy ( J:208675 )

• mice show forebrain weight loss and measurable cortical and striatal volume loss at 12 months

abnormal neuron morphology ( J:157723 )

• at 12 months, mice exhibit protein aggregates in the cortex and striatum unlike in wild-type mice

neuronal intranuclear inclusions ( J:137345 )

• at 12 and 18 months, large mutant huntingtin (mhtt) protein inclusions are detected in deep cortical layers with smaller inclusions found in the upper cortical layers with very few small inclusions in striatal neurons

neurodegeneration ( J:137345 )

• evident at 12 months in transgenic mice, but not in wild-type

neuron degeneration ( J:137345 , J:157723 )

• striatal neuron degeneration is observed at 12 months, but not in wild-type brains (J:137345)

• at 12 months, mice exhibit selective neuropathy unlike wild-type mice (J:157723)

abnormal nervous system electrophysiology ( J:137345 )

• medium and large amplitude spontaneous currents in medium spiny neurons (MSNs) are reduced compared to wild-type, while probability of occurrence of small amplitude events is significantly elevated

decreased excitatory postsynaptic current frequency ( J:208675 )

• spontaneous EPSCs are reduced in frequency (at 5-15 pA) in medium spiny neurons (MSNs) in striatal slices from 10-11 month-old animals compared to wild-type

reduced NMDA-mediated synaptic currents ( J:208675 )

• evoked synaptic NMDA currents in medium spiny neurons (MSNs) in striatal slices from 13-15 month-old mice are significantly impaired compared to wild-type; normalized amplitudes of currents are reduced

abnormal inhibitory postsynaptic currents ( J:208675 )

• spontaneous IPSCs are increased in medium spiny neurons (MSNs) in striatal slices from 10-11 month-old animals compared to wild-type

decreased prepulse inhibition ( J:185262 )

• observed at 36 and 52 weeks of age in females and 28 and 52 weeks in males

behavior/neurological

behavior/neurological phenotype ( J:185262 )

N • mice do exhibit a deterioration in grip strength as compared to controls

abnormal depression-related behavior ( J:157723 )

• at 12 months, mice exhibit depressive-like behavior unlike wild-type mice

behavioral despair ( J:208675 )

• mice exhibit depression-like behavior (assayed in forced swim test)

increased anxiety-related response ( J:157723 , J:185262 , J:208675 )

• increased preference for dark in dark/light choice test starting at 12 weeks of age (J:185262)

• males prefer dark at 4 weeks (J:185262)

• displayed in light-dark box test (J:208675)

decreased startle reflex ( J:185262 )

• observed at 24 and 36 weeks of age in females and 36 weeks in males

impaired coordination ( J:137345 , J:157723 , J:185262 , J:208675 )

• at 2, 6 and 12 months, transgenics display decline in performance in rotating rod tests, compared to wild-type controls; performance declines with increasing age in mutants, but age has no effect in controls (J:137345)

• starting at 2 months and worsening with age (J:157723)

• mice exhibit a progressive impairment on the rotarod test beginning at 4 weeks of age (J:185262)

• progressive rotarod deficit is observed between 2 and 6 months; progression is smaller but still significant from 6-12 months (J:208675)

abnormal gait ( J:185262 )

• wider base (separation between legs) at 36 weeks

short stride length ( J:185262 )

• shorter splay length (contralateral) at 12 weeks, but longer splay at 36 weeks

decreased vertical activity ( J:185262 )

• mice rear less in the center of the open field test than controls in light and dark phases at all ages

• mice exhibit a decrease in climbing activity with many mice not climbing at all

decreased locomotor activity ( J:185262 )

• mice cover less total distance in light and dark phases of open field test starting at 28 weeks of age

• mice cover less distance in center starting at 28weeks in light phase

growth/size/body

increased body weight ( J:137345 , J:185262 )

• mice show significant weight gain of 20-30% over control weights in the 2-12 month period of testing (J:137345)

• body weight is significantly increased in females at 12 weeks and in males at 16 weeks of age (J:185262)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:137345