Phenotypes Associated with This Genotype

Genotype
MGI:3694681

• Allelic Composition: Tg(HDexon1)62Gpb/0
• Genetic Background: B6CBA-Tg(HDexon1)62Gpb/1J

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

cardiovascular system

abnormal myocardial fiber morphology ( J:116660 )

• mitochondria in cardiomyocytes examined at 12 weeks of age exhibit a circular appearance with a disruption of uniform densities

decreased heart weight ( J:116660 )

• significantly reduced at 12 weeks of age

dilated heart left ventricle ( J:116660 )

• mice exhibit left ventricular dilation in comparison to controls

decreased cardiac output ( J:116660 )

• detected as early as 8 weeks of age and reduced to 50% by 12 weeks of age

decreased cardiac stroke volume ( J:116660 )

• mice exhibit progressive reduction in stroke volume, although there are no differences in heart rate

abnormal diastolic filling velocity ( J:116660 )

• 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

decreased ventricle muscle contractility ( J:116660 )

• diminished left ventricular wall motion during systole

• left ventricle fractional shortening significantly impaired at 10 and 12 weeks of age

decreased left ventricle systolic pressure ( J:116660 )

• diminished left ventricular wall motion during systole

• left ventricle fractional shortening significantly impaired at 10 and 12 weeks of age

growth/size/body

slow postnatal weight gain ( J:116660 )

• mice exhibited less weight gain over time than controls

weight loss ( J:99425 )

muscle

abnormal myocardial fiber morphology ( J:116660 )

• mitochondria in cardiomyocytes examined at 12 weeks of age exhibit a circular appearance with a disruption of uniform densities

decreased ventricle muscle contractility ( J:116660 )

• 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

abnormal voluntary movement ( J:99425 )

• impaired mobility in home cages

nervous system

abnormal striatum morphology ( J:111237 )

• 3-hydroxykynurenine (3-HK) levels are significantly elevated in the striatum at 4 weeks of age, a phenotype observed in Huntington disease patients

abnormal cerebral cortex morphology ( J:111237 )

• 3-HK levels are significantly elevated in the cortex at 4 weeks of age, a phenotype observed in Huntington disease patients

abnormal cerebellum morphology ( J:111237 )

• 3-HK levels are significantly elevated in the cerebellum at 4 weeks of age, a phenotype observed in Huntington disease patients

abnormal nervous system physiology ( J:99425 )

• 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

abnormal neuron physiology ( J:76018 )

• 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