Mouse Genome Informatics
cn1
    Emx1tm1(cre)Ito/Emx1+
Rgs9tm1(cre)Yql/Rgs9+
Tg(HTT*97Q)IXwy/0

involves: 129P2/OlaHsd * FVB
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
N
• depression-like phenotype is not significantly different from wild-type but is significantly improved compared to BACHD (Tg(HTT*97Q)IXwy) mice
• anxiety response is significantly improved compared to BACHD mice
• significant, consistent improvement is observed in hypoactivity phenotype at 6 and 12 months compared to BACHD mice
• significant, consistent improvement in coordination is observed at 6 and 12 months compared to BACHD mice

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


Mouse Genome Informatics
cn2
    Emx1tm1(cre)Ito/Emx1+
Tg(HTT*97Q)IXwy/0

involves: 129P2/OlaHsd * FVB
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
N
• depression-like phenotype is not significantly different from wild-type but is significantly improved compared to BACHD (Tg(HTT*97Q)IXwy) mice
• anxiety response is significantly improved compared to BACHD mice
• 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
• 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
N
• no significant difference is observed in forebrain weight or cortical or striatal volume between either wild-type or BACHD mice
• 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
• spontaneous excitatory postsynaptic currents (sEPSCs) and spontaneous inhibitory postsynaptic currents (sEPSCs) in striatal medium spiny neurons (MSNs) are improved relative to BACHD neurons


Mouse Genome Informatics
cn3
    Rgs9tm1(cre)Yql/Rgs9+
Tg(HTT*97Q)IXwy/0

involves: FVB
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• significantly different from wild-type (similar to BACHD (Tg(HTT*97Q)IXwy) mice); little improvement is observed
• significantly different from wild-type (similar to BACHD mice); little improvement is observed
• mice show significant rotarod impairment between 6 and 12 months relative to wild-type
• reduced movement is observed at 12 months relative to wild-type

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


Mouse Genome Informatics
cx4
    Htttm1Hay/Htttm1Hay
Tg(HTT*97Q)IXwy/0
Tg(YAC18)18Hay/Tg(YAC18)18Hay

FVB.Cg-Htttm1Hay Tg(HTT*97Q)IXwy Tg(YAC18)18Hay
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• 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 Htttm1Hay, indicating increased depressive-like behavior
• 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 Htttm1Hay, 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 Htttm1Hay, indicating increased anxiety
• 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 Htttm1Hay
• at 9 months of age, mice show deficits in object recognition by preference for an unknown object
• 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
• 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 Htttm1Hay
• in longitudinal rotarod testing, mice exhibit declining performance with age
• mice show increased stereotypy, or repetitive movement, and decreased jumping compared to mice homozygous for Tg(YAC18)18Hay and Htttm1Hay
• however, no difference in distance traveled or ambulation time is seen during spontaneous activity

growth/size/body
• 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 Htttm1Hay
• body weight gain is greater in females than in males

nervous system
• mice show a trend towards reduced forebrain weight at 12 months of age
• mice show a trend toward reduced corpus callosum volume at 12 months of age
• mice show reductions in both striatal volume and cortical volume at 12 months of age
• 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
• mice exhibit progressive hippocampal synaptic plasticity deficit
• at 9 months of age, striatal spiny projection neurons exhibit small changes in membrane properties
• 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
• at 9 months of age, striatal spiny projection neurons exhibit lower amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs)
• 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
• paired-pulse facilitation in the hippocampus is reduced at 9 months of age indicating impaired short-term plasticity

Mouse Models of Human Disease
OMIM IDRef(s)
Huntington Disease; HD 143100 J:191147 , J:215223


Mouse Genome Informatics
tg5
    Tg(HTT*97Q)IXwy/0
FVB-Tg(HTT*97Q)IXwy
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
N
• cerebellar weight does not differ from wild-type
• at 12 months, forebrain weight (whole brain minus cerebellum and olfactory bulb) is 20% lower than wild-type controls; however cerebellar weight is comparable
• mice exhibit decreased forebrain weight loss compared with wild-type mice
• at 12 months, robust decrease in striatal volume (28% of wild-type) is observed
• at 12 months, robust decrease in cerebral cortex volume (32% of wild-type) is observed
• at 6 months of age, brains do not display any obvious pathology, but at 12 months, brains are visibly atrophic compared to wild-type
• mice show forebrain weight loss and measurable cortical and striatal volume loss at 12 months
• at 12 months, mice exhibit protein aggregates in the cortex and striatum unlike in wild-type mice
• 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
• evident at 12 months in transgenic mice, but not in wild-type
• 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)
• 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
• 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
• 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
• spontaneous IPSCs are increased in medium spiny neurons (MSNs) in striatal slices from 10-11 month-old animals compared to wild-type
• observed at 36 and 52 weeks of age in females and 28 and 52 weeks in males

behavior/neurological
N
• mice do exhibit a deterioration in grip strength as compared to controls
• at 12 months, mice exhibit depressive-like behavior unlike wild-type mice
• mice exhibit depression-like behavior (assayed in forced swim test)
• 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)
• observed at 24 and 36 weeks of age in females and 36 weeks in males
• 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)
• 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
• 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
• wider base (separation between legs) at 36 weeks
• shorter splay length (contralateral) at 12 weeks, but longer splay at 36 weeks

growth/size/body
• 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
OMIM IDRef(s)
Huntington Disease; HD 143100 J:137345