Mouse Genome Informatics
tg
    Tg(HD)63Aron/?
involves: C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
nervous system
• htt staining is substantially increased in the cytoplasm of striatal neurons as compared to control
• 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
• 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
• dendrites in spiny neurons have significantly more curved endings (J-dendrites) and sharp bends (wavy dendrites) than control
• 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
• 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
• 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
• 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
• most mice exhibit clasping in the tail suspension test
• in rotarod performance
• some mice exhibit an alteration in activity that is scored as hypo- or hyperactivity
• 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
OMIM IDRef(s)
Huntington Disease; HD 143100 J:72772