cardiovascular system
• mitochondria in cardiomyocytes examined at 12 weeks of age exhibit a circular appearance with a disruption of uniform densities
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• significantly reduced at 12 weeks of age
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• mice exhibit left ventricular dilation in comparison to controls
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• detected as early as 8 weeks of age and reduced to 50% by 12 weeks of age
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• mice exhibit progressive reduction in stroke volume, although there are no differences in heart rate
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• transmitral flow velocity is altered as compared to controls
• E/A ratio is significantly decreased at all time points
• mice exhibit a decrease in passive ventricular filling and a significant increase in atrial-mediated left ventricle filling
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• diminished left ventricular wall motion during systole
• left ventricle fractional shortening significantly impaired at 10 and 12 weeks of age
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• diminished left ventricular wall motion during systole
• left ventricle fractional shortening significantly impaired at 10 and 12 weeks of age
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growth/size/body
• mice exhibited less weight gain over time than controls
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weight loss
(
J:99425
)
muscle
• mitochondria in cardiomyocytes examined at 12 weeks of age exhibit a circular appearance with a disruption of uniform densities
|
• diminished left ventricular wall motion during systole
• left ventricle fractional shortening significantly impaired at 10 and 12 weeks of age
|
behavior/neurological
limb grasping
(
J:99425
)
• exhibit clasping of both fore and hind paws
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• impaired mobility in home cages
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nervous system
• 3-hydroxykynurenine (3-HK) levels are significantly elevated in the striatum at 4 weeks of age, a phenotype observed in Huntington disease patients
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• 3-HK levels are significantly elevated in the cortex at 4 weeks of age, a phenotype observed in Huntington disease patients
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• 3-HK levels are significantly elevated in the cerebellum at 4 weeks of age, a phenotype observed in Huntington disease patients
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• striatal and cortical mitochondria are equally resistant to calcium at 8 and 12 weeks of age, while in controls, striatal mitochondria is more sensitive to calcium
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• striatal and cortical neurons display more rapid and increased swelling to N-methyl-D-aspartate (NMDA) than controls, but not to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) or kainate (KA), indicating increased sensitivity to NMDA
• intracellular recordings show that resting membrane potentials of striatal neurons are significantly more depolarized than in controls
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
Huntington's disease | DOID:12858 |
OMIM:143100 |
J:99425 , J:111237 |