Phenotypes Associated with This Genotype

Genotype
MGI:3613525

• Allelic Composition: Tg(YAC128)53Hay/0
• Genetic Background: FVB/N-Tg(YAC128)53Hay

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

nervous system

increased susceptibility to neuronal excitotoxicity ( J:105723 )

• in medium spiny neurons in response to NMDA (500 um) exposure compared to wild-type mice or mice carrying Tg(YAC128)55Hay

decreased brain weight ( J:84453 , J:120991 )

• total brain weight decreases by 5% at 9 months, progressing to a 10% decrease by 1 year (J:84453)

• cerebellum weight is unchanged (J:84453)

• reduced compared to wild-type controls at 18 months (0.35 grams vs 0.38 grams) (J:120991)

abnormal basal ganglion morphology ( J:84453 )

• mean area of striatal neurons is decreased by 18% in 12 month old mice

• striatal volume is decreased by 15% by 9 months of age

abnormal striatum morphology ( J:105723 , J:111237 , J:120991 )

• loss of striatal neurons (J:105723)

• decrease in striatal volume at 12 months of age (J:105723)

• the levels of both the endogenous excitotoxin quinolinic acid (QUIN) and its bioprecursor, 3-hydroxykynurenine (3-HK) are increased in the striatum beginning at 8 months of age, similarly to that seen in Huntington disease patients (J:111237)

• reduced compared to wild-type controls at 18 months (10.9 mm³ vs 12.3 mm³) (J:120991)

• significant volume loss is detected at 12 months compared to wild-type controls (J:120991)

• neuronal loss is observed at 12 months relative to controls (J:120991)

• diffuse huntingtin (htt) fragments showing nuclear localization in striatum at 3 months, and this increases with age such that at 12 months, most striatal neurons are positive for htt (J:120991)

abnormal medium spiny neuron morphology ( J:84453 )

• medium spiny neurons (MSN) are decreased 8% by 9 months of age

loss of basal ganglia neurons ( J:84453 )

• transgenic mice exhibit a 9% decrease in striatal neurons by 9 months, progressing to a 15-18% loss by 12 months

• medium spiny neurons (MSN), the major neuronal cell type of the straitum, are decreased 8% by 9 months of age

abnormal cerebral cortex morphology ( J:84453 , J:111237 )

• cortex volume decreased by 7% by 12 months of age (J:84453)

• QUIN and 3-HK levels are elevated in the cerebral cortex, similarly to that seen in Huntington disease patients (J:111237)

neuronal intranuclear inclusions ( J:84453 , J:105723 )

• neuronal inclusions observed throughout nucleoplasm of all striatal cells by 18 months of age (J:84453)

• at 18 months of age in the striatum and cortex (J:105723)

behavior/neurological

abnormal learning/memory/conditioning ( J:105723 )

• cognitive deficits including difficulties in changing strategies and delayed platform finding beginning at 2 months of age

abnormal motor learning ( J:105723 )

• impaired in a rotarod assay beginning at 2 months of age

abnormal motor capabilities/coordination/movement ( J:105723 )

• motor abnormalities similar to those seen in the clinical course of Huntington disease

• disease progression is accelerated compared to mice hemizygous for Tg(YAC128)55Hay

impaired coordination ( J:84453 , J:105723 , J:120991 )

• progressive decrease in fixed speed rotarod performance beginning at 6 months of age (J:84453)

• in a rotarod assay beginning after 3 months of age and becoming worse with age (J:105723)

• significant deficit in rotarod tests at 2 months of age (J:120991)

decreased locomotor activity ( J:84453 , J:105723 )

• hypokinetic phenotype observed beginning at 6 months of age and becoming significant by 12 months of age in open field apparatus (J:84453)

• beginning after 3 months of age as measured by decrease in spontaneous ambulation in open-field testing (J:105723)

hyperactivity ( J:84453 , J:105723 )

• hyperkinetic phenotype observed at 3 months in open field apparatus (J:84453)

• at 2 months of age (J:105723)

bradykinesia ( J:120991 )

• starting at 4 months of age, a hypokinetic phenotype is displayed compared to wild-type controls in open field test

growth/size/body

increased body weight ( J:84453 )

cellular

increased susceptibility to neuronal excitotoxicity ( J:105723 )

• in medium spiny neurons in response to NMDA (500 um) exposure compared to wild-type mice or mice carrying Tg(YAC128)55Hay

homeostasis/metabolism

increased susceptibility to neuronal excitotoxicity ( J:105723 )

• in medium spiny neurons in response to NMDA (500 um) exposure compared to wild-type mice or mice carrying Tg(YAC128)55Hay

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:84453 , J:105723 , J:111237