Phenotypes Associated with This Genotype

Genotype
MGI:3723505

• Allelic Composition: Tg(HD)63Aron/?
• Genetic Background: involves: C57BL/6 * SJL

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

nervous system

abnormal striatum morphology ( J:72772 )

• htt staining is substantially increased in the cytoplasm of striatal neurons as compared to control

abnormal cerebral cortex morphology ( J:72772 )

• cytoplasmic huntingtin accumulation is prevalent in neurons of the frontal and cingulated cortices and occasionally present in the piriform and hippocampal cortices

• cortical pyramidal neurons exhibit retraction and disorientation of the apical dendrite, as well as dendritic abnormalities such as beading, small sharp bends, misalignment and bifurcation

abnormal neuron morphology ( J:72772 )

• one severely affected mouse exhibited shrunken neurons in the hippocampus and cerebellum

• intracytoplasmic vacuoles and plasma membrane blebs appear in cell bodies and dendrites of neurons with an accumulation of huntingtin

abnormal medium spiny neuron morphology ( J:72772 )

• dendrites in spiny neurons have significantly more curved endings (J-dendrites) and sharp bends (wavy dendrites) than control

abnormal dendrite morphology ( J:72772 )

• cortical pyramidal neurons exhibit retraction and disorientation of the apical dendrite, as well as dendritic abnormalities such as beading, small sharp bends, misalignment and bifurcation

• some, but not all, mice exhibit dysmorphic dendrites in hippocampal pyramidal neurons

• one severely affected mouse had dysmorphic dendrites in cerebellar Purkinje cells

• dendrites in spiny neurons have significantly more curved endings (J-dendrites) and sharp bends (wavy dendrites) than control

neuronal intranuclear inclusions ( J:72772 )

• intranuclear inclusions are detected in the cytoplasm of cortical neurons and to a lesser degree in striatal neurons

• in a sample of five mice, 27-70% of large striatal neurons that labeled for huntingtin had inclusions

• nuclear inclusions are composed of granules and filaments as determined by electron microscopy

• in 11 of 14 mice, inclusions appeared in a few cells in the hippocampus, substantia nigra, cerebellum and brainstem

abnormal excitatory postsynaptic potential ( J:72772 )

• stimulation of corpus callosum slices evoked smaller EPSPs in striatal neurons as compared to control

• response to stimulus in striatal neurons results in a rightward shift in the input-output curve (EPSP amplitude) as compared to control

enhanced NMDA-mediated synaptic currents ( J:72772 )

• one population of mutant neurons (most affected) exhibit higher peak currents and current densities when induced by NMDA as well as an increase in calcium ion influx

behavior/neurological

limb grasping ( J:72772 )

• most mice exhibit clasping in the tail suspension test

impaired coordination ( J:72772 )

• in rotarod performance

abnormal locomotor activation ( J:72772 )

• some mice exhibit an alteration in activity that is scored as hypo- or hyperactivity

abnormal gait ( J:72772 )

• some mice exhibit an abnormal gait which could include wide-based gait, walking with an arched posture and slow gait

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:72772