Phenotypes Associated with This Genotype

Genotype
MGI:5617271

• Allelic Composition: Htt^tm1Hay/Htt^tm1Hay; Tg(HTT*97Q)IXwy/0; Tg(YAC18)18Hay/Tg(YAC18)18Hay
• Genetic Background: FVB.Cg-Htt^tm1Hay Tg(HTT*97Q)IXwy Tg(YAC18)18Hay

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

behavior/neurological

abnormal motor learning ( J:191147 )

• 2 month old mice exhibit increased falls and decreased latency to fall during rotarod training, indicating a motor learning deficit

• males show an overall greater impairment on the rotarod than males homozygous for Tg(YAC18)18Hay and Htt^tm1Hay

abnormal object recognition memory ( J:191147 )

• at 9 months of age, mice show deficits in object recognition by preference for an unknown object

impaired spatial learning ( J:191147 )

• at 6 and 9 months of age, mice show a spatial deficit in spatial learning by preference for a known object in a novel location

abnormal depression-related behavior ( J:191147 )

• mice spend more time being immobile and less time swimming in the Porsolt forced swim test compared to mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay, indicating increased depressive-like behavior

increased thigmotaxis ( J:191147 )

• during open-field exploration, mice enter the center of the field less frequently and spend less total time in the center of the field compared to mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay, indicating increased anxiety

• in the elevated plus maze, mice spend less time in the open arms and dip their head off the edges of the open arms less frequently than mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay, indicating increased anxiety

abnormal motor capabilities/coordination/movement ( J:191147 )

• during a spontaneous climbing test, 2 month old mice trend toward an increased latency to begin climbing and decreased number of climbing events and spend significantly less time climbing than mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay

impaired coordination ( J:191147 )

• in longitudinal rotarod testing, mice exhibit declining performance with age

increased stereotypic behavior ( J:191147 )

• mice show increased stereotypy, or repetitive movement, and decreased jumping compared to mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay

• however, no difference in distance traveled or ambulation time is seen during spontaneous activity

growth/size/body

increased body weight ( J:191147 )

• increase in body weight compared to wild-type controls and a small increase in body weight compared to mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay

• body weight gain is greater in females than in males

nervous system

abnormal forebrain morphology ( J:191147 )

• mice show a trend towards reduced forebrain weight at 12 months of age

abnormal corpus callosum morphology ( J:191147 )

• mice show a trend toward reduced corpus callosum volume at 12 months of age

abnormal striatum morphology ( J:191147 )

• mice show reductions in both striatal volume and cortical volume at 12 months of age

abnormal action potential ( J:215223 )

• at 9 months of age, striatal spiny projection neurons show a significant depolarization of the resting membrane potential and elevated action potential threshold, however excitability of these neurons is similar to controls

• action potential threshold of striatal spiny projection neurons is already increased at 6 months of age

impaired synaptic plasticity ( J:215223 )

• mice exhibit progressive hippocampal synaptic plasticity deficit

abnormal CNS synaptic transmission ( J:215223 )

• at 9 months of age, striatal spiny projection neurons exhibit small changes in membrane properties

decreased excitatory postsynaptic current amplitude ( J:215223 )

• at 9 months of age, striatal spiny projection neurons exhibit lower amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs)

decreased excitatory postsynaptic current frequency ( J:215223 )

• at 9 months of age, striatal spiny projection neurons exhibit lower frequency of spontaneous excitatory postsynaptic currents (sEPSCs)

• however, release probability from presynaptic terminals is unaltered

reduced long-term potentiation ( J:215223 )

• mice exhibit a deficiency in long-term potentiation at CA3-to-CA1 synapses at 9 months of age but not at 3 months of age

decreased paired-pulse facilitation ( J:215223 )

• paired-pulse facilitation in the hippocampus is reduced at 9 months of age indicating impaired short-term plasticity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:191147 , J:215223