Mouse Genome Informatics
tg
    Tg(YAC128)53Hay/0
FVB/N-Tg(YAC128)53Hay
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
nervous system
• in medium spiny neurons in response to NMDA (500 um) exposure compared to wild-type mice or mice carrying Tg(YAC128)55Hay
• total brain weight decreases by 5% at 9 months, progressing to a 10% decrease by 1 year (J:84453)
• cerebellum weight is unchanged (J:84453)
• reduced compared to wild-type controls at 18 months (0.35 grams vs 0.38 grams) (J:120991)
• mean area of striatal neurons is decreased by 18% in 12 month old mice
• striatal volume is decreased by 15% by 9 months of age
• loss of striatal neurons (J:105723)
• decrease in striatal volume at 12 months of age (J:105723)
• the levels of both the endogenous excitotoxin quinolinic acid (QUIN) and its bioprecursor, 3-hydroxykynurenine (3-HK) are increased in the striatum beginning at 8 months of age, similarly to that seen in Huntington disease patients (J:111237)
• reduced compared to wild-type controls at 18 months (10.9 mm3 vs 12.3 mm3) (J:120991)
• significant volume loss is detected at 12 months compared to wild-type controls (J:120991)
• neuronal loss is observed at 12 months relative to controls (J:120991)
• diffuse huntingtin (htt) fragments showing nuclear localization in striatum at 3 months, and this increases with age such that at 12 months, most striatal neurons are positive for htt (J:120991)
• medium spiny neurons (MSN) are decreased 8% by 9 months of age
• transgenic mice exhibit a 9% decrease in striatal neurons by 9 months, progressing to a 15-18% loss by 12 months
• medium spiny neurons (MSN), the major neuronal cell type of the straitum, are decreased 8% by 9 months of age
• cortex volume decreased by 7% by 12 months of age (J:84453)
• QUIN and 3-HK levels are elevated in the cerebral cortex, similarly to that seen in Huntington disease patients (J:111237)
• neuronal inclusions observed throughout nucleoplasm of all striatal cells by 18 months of age (J:84453)
• at 18 months of age in the striatum and cortex (J:105723)

behavior/neurological
• cognitive deficits including difficulties in changing strategies and delayed platform finding beginning at 2 months of age
• impaired in a rotarod assay beginning at 2 months of age
• motor abnormalities similar to those seen in the clinical course of Huntington disease
• disease progression is accelerated compared to mice hemizygous for Tg(YAC128)55Hay
• progressive decrease in fixed speed rotarod performance beginning at 6 months of age (J:84453)
• in a rotarod assay beginning after 3 months of age and becoming worse with age (J:105723)
• significant deficit in rotarod tests at 2 months of age (J:120991)
• starting at 4 months of age, a hypokinetic phenotype is displayed compared to wild-type controls in open field test
• hyperkinetic phenotype observed at 3 months in open field apparatus (J:84453)
• at 2 months of age (J:105723)
• hypokinetic phenotype observed beginning at 6 months of age and becoming significant by 12 months of age in open field apparatus (J:84453)
• beginning after 3 months of age as measured by decrease in spontaneous ambulation in open-field testing (J:105723)

growth/size/body

cellular
• in medium spiny neurons in response to NMDA (500 um) exposure compared to wild-type mice or mice carrying Tg(YAC128)55Hay

homeostasis/metabolism
• in medium spiny neurons in response to NMDA (500 um) exposure compared to wild-type mice or mice carrying Tg(YAC128)55Hay

Mouse Models of Human Disease
OMIM IDRef(s)
Huntington Disease; HD 143100 J:84453 , J:105723 , J:111237