Mouse Genome Informatics
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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
• 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
• 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
• observed at 36 and 52 weeks of age in females and 28 and 52 weeks in males
• 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)

• mice do exhibit a deterioration in grip strength as compared to controls (J:185262)
• at 12 months, mice exhibit depressive-like behavior unlike wild-type mice
• 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)
• 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)
• 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

• 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
Huntington Disease; HD 143100 J:137345