Phenotypes associated with this allele

• Allele Symbol: Tg(HTT*97Q)IXwy
• Allele Name: transgene insertion I, X William Yang
• Allele ID: MGI:3800779
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Emx1^tm1(cre)Ito/Emx1^+ Rgs9^tm1.1(cre)Yql/Rgs9^+ Tg(HTT*97Q)IXwy/0	involves: 129P2/OlaHsd * FVB	MGI:5564936
cn2	Emx1^tm1(cre)Ito/Emx1^+ Tg(HTT*97Q)IXwy/0	involves: 129P2/OlaHsd * FVB	MGI:5564938
cn3	Rgs9^tm1.1(cre)Yql/Rgs9^+ Tg(HTT*97Q)IXwy/0	involves: FVB	MGI:5564939
cx4	Htt^tm1Hay/Htt^tm1Hay Tg(HTT*97Q)IXwy/0 Tg(YAC18)18Hay/Tg(YAC18)18Hay	FVB.Cg-Htt^tm1Hay Tg(HTT*97Q)IXwy Tg(YAC18)18Hay	MGI:5617271
tg5	Tg(HTT*97Q)IXwy/0	FVB-Tg(HTT*97Q)IXwy	MGI:3800927

Genotype
MGI:5564936

cn1

• Allelic Composition: Emx1^tm1(cre)Ito/Emx1⁺; Rgs9^{tm1.1(cre)Yql}/Rgs9⁺; Tg(HTT*97Q)IXwy/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

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

behavior/neurological

behavior/neurological phenotype ( J:208675 )

N • depression-like phenotype is not significantly different from wild-type but is significantly improved compared to BACHD (Tg(HTT*97Q)IXwy) mice

N • anxiety response is significantly improved compared to BACHD mice

N • significant, consistent improvement is observed in hypoactivity phenotype at 6 and 12 months compared to BACHD mice

N • significant, consistent improvement in coordination is observed at 6 and 12 months compared to BACHD mice

nervous system

nervous system phenotype ( J:208675 )

N • forebrain weight loss and cortical/striatal volume loss are improved relative to BACHD (Tg(HTT*97Q)IXwy) mice

Genotype
MGI:5564938

cn2

• Allelic Composition: Emx1^tm1(cre)Ito/Emx1⁺; Tg(HTT*97Q)IXwy/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

behavior/neurological

behavior/neurological phenotype ( J:208675 )

N • depression-like phenotype is not significantly different from wild-type but is significantly improved compared to BACHD (Tg(HTT*97Q)IXwy) mice

N • anxiety response is significantly improved compared to BACHD mice

impaired coordination ( J:208675 )

• mice show rotarod impairment relative to wild-type at 6 and 12 months; significant partial improvement is observed by 6 months compared to BACHD mice

decreased locomotor activity ( J:208675 )

• reduced movement is observed at 12 months compared to wild-type; significant partial improvement in the open-field is observed at 12 months compared to BACHD mice

nervous system

nervous system phenotype ( J:208675 )

N • no significant difference is observed in forebrain weight or cortical or striatal volume between either wild-type or BACHD mice

N • evoked synaptic NMDA currents in medium spiny neurons (MSNs) in striatal slices from 13-15 month-old mice are not significantly different from wild-type; normalized amplitudes of currents are not significantly different

N • spontaneous excitatory postsynaptic currents (sEPSCs) and spontaneous inhibitory postsynaptic currents (sEPSCs) in striatal medium spiny neurons (MSNs) are improved relative to BACHD neurons

Genotype
MGI:5564939

cn3

• Allelic Composition: Rgs9^{tm1.1(cre)Yql}/Rgs9⁺; Tg(HTT*97Q)IXwy/0
• Genetic Background: involves: FVB

behavior/neurological

behavioral despair ( J:208675 )

• significantly different from wild-type (similar to BACHD (Tg(HTT*97Q)IXwy) mice); little improvement is observed

increased anxiety-related response ( J:208675 )

• significantly different from wild-type (similar to BACHD mice); little improvement is observed

impaired coordination ( J:208675 )

• mice show significant rotarod impairment between 6 and 12 months relative to wild-type

decreased locomotor activity ( J:208675 )

• reduced movement is observed at 12 months relative to wild-type

nervous system

nervous system phenotype ( J:208675 )

N • evoked synaptic NMDA currents in medium spiny neurons (MSNs) in striatal slices from 13-15 month-old mice are not significantly different from wild-type; normalized amplitudes of currents are not significantly different

forebrain atrophy ( J:208675 )

• forebrain weight loss and striatal volume loss) are observed at 12 months compared to wild-type

Genotype
MGI:5617271

cx4

• Allelic Composition: Htt^tm1Hay/Htt^tm1Hay; Tg(HTT*97Q)IXwy/0; Tg(YAC18)18Hay/Tg(YAC18)18Hay
• Genetic Background: FVB.Cg-Htt^tm1Hay Tg(HTT*97Q)IXwy Tg(YAC18)18Hay

behavior/neurological

abnormal motor learning ( J:191147 )

• 2 month old mice exhibit increased falls and decreased latency to fall during rotarod training, indicating a motor learning deficit

• males show an overall greater impairment on the rotarod than males homozygous for Tg(YAC18)18Hay and Htt^tm1Hay

abnormal object recognition memory ( J:191147 )

• at 9 months of age, mice show deficits in object recognition by preference for an unknown object

impaired spatial learning ( J:191147 )

• at 6 and 9 months of age, mice show a spatial deficit in spatial learning by preference for a known object in a novel location

abnormal depression-related behavior ( J:191147 )

• mice spend more time being immobile and less time swimming in the Porsolt forced swim test compared to mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay, indicating increased depressive-like behavior

increased thigmotaxis ( J:191147 )

• during open-field exploration, mice enter the center of the field less frequently and spend less total time in the center of the field compared to mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay, indicating increased anxiety

• in the elevated plus maze, mice spend less time in the open arms and dip their head off the edges of the open arms less frequently than mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay, indicating increased anxiety

abnormal motor capabilities/coordination/movement ( J:191147 )

• during a spontaneous climbing test, 2 month old mice trend toward an increased latency to begin climbing and decreased number of climbing events and spend significantly less time climbing than mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay

impaired coordination ( J:191147 )

• in longitudinal rotarod testing, mice exhibit declining performance with age

increased stereotypic behavior ( J:191147 )

• mice show increased stereotypy, or repetitive movement, and decreased jumping compared to mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay

• however, no difference in distance traveled or ambulation time is seen during spontaneous activity

growth/size/body

increased body weight ( J:191147 )

• increase in body weight compared to wild-type controls and a small increase in body weight compared to mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay

• body weight gain is greater in females than in males

nervous system

abnormal forebrain morphology ( J:191147 )

• mice show a trend towards reduced forebrain weight at 12 months of age

abnormal corpus callosum morphology ( J:191147 )

• mice show a trend toward reduced corpus callosum volume at 12 months of age

abnormal striatum morphology ( J:191147 )

• mice show reductions in both striatal volume and cortical volume at 12 months of age

abnormal action potential ( J:215223 )

• at 9 months of age, striatal spiny projection neurons show a significant depolarization of the resting membrane potential and elevated action potential threshold, however excitability of these neurons is similar to controls

• action potential threshold of striatal spiny projection neurons is already increased at 6 months of age

impaired synaptic plasticity ( J:215223 )

• mice exhibit progressive hippocampal synaptic plasticity deficit

abnormal CNS synaptic transmission ( J:215223 )

• at 9 months of age, striatal spiny projection neurons exhibit small changes in membrane properties

decreased excitatory postsynaptic current amplitude ( J:215223 )

• at 9 months of age, striatal spiny projection neurons exhibit lower amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs)

decreased excitatory postsynaptic current frequency ( J:215223 )

• at 9 months of age, striatal spiny projection neurons exhibit lower frequency of spontaneous excitatory postsynaptic currents (sEPSCs)

• however, release probability from presynaptic terminals is unaltered

reduced long-term potentiation ( J:215223 )

• mice exhibit a deficiency in long-term potentiation at CA3-to-CA1 synapses at 9 months of age but not at 3 months of age

decreased paired-pulse facilitation ( J:215223 )

• paired-pulse facilitation in the hippocampus is reduced at 9 months of age indicating impaired short-term plasticity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:191147 , J:215223

Genotype
MGI:3800927

tg5

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

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