Phenotypes Associated with This Genotype

Genotype
MGI:5635158

• Allelic Composition: Tg(HTT*)NXwy/0
• Genetic Background: involves: FVB/NJ

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

behavior/neurological

abnormal depression-related behavior ( J:219890 )

• mice show increased immobility in the forced swim test at 5 months of age, suggesting presence of depression-like behavior

poor grooming ( J:219890 )

• mice at 10-11 months of age are frequently found lying upside down in their home cage, poorly groomed

dystonia ( J:219890 )

• mice show sustained retroflex of head and neck indicating cervical dystonia at 11 months of age

impaired coordination ( J:219890 )

• in the accelerating rotarod test, mice exhibit progressive impairment at 2 and 6 months of age and by 8 months of age, mice can no longer run on it

abnormal head movements ( J:219890 )

• mice show frequent abnormal head movements at 11 months of age, consisting of smooth but non-rhythmic swinging of the head and upper body indicating choreiform movement, and sustained retroflex of head and neck indicating cervical dystonia

• onset of abnormal head movements is around 7 months of age and increases progressively

abnormal gait ( J:219890 )

• gait abnormalities are seen at 8 months of age

• starting around 10 months of age, mutants show frequent spontaneous falls

astasia ( J:219890 )

• mice at 10-11 months of age are frequently found lying upside down in their home cage

decreased vertical activity ( J:219890 )

• in the open field test, mice show impairment in vertical plane entry at 8, but not 2, months of age

decreased locomotor activity ( J:219890 )

• in the open field test, mice show impairment in horizontal distance traveled, and horizontal speed at 8, but not 2, months of age

endocrine/exocrine glands

testicular atrophy ( J:219890 )

♂ • in 10 month old mice

growth/size/body

weight loss ( J:219890 )

• mice exhibit significant weight loss at 10 and 11 months of age

increased body weight ( J:219890 )

• both males and females are heavier than wild-type mice at 2 and 6 months of age

immune system

CNS inflammation ( J:219890 )

• gene expression profiling indicates progressive neuroinflammation

muscle

dystonia ( J:219890 )

• mice show sustained retroflex of head and neck indicating cervical dystonia at 11 months of age

skeletal muscle fiber atrophy ( J:219890 )

• atrophy, reduction of muscle fiber caliber and aberrant central localization of nuclei within the fiber of quadriceps muscle

nervous system

CNS inflammation ( J:219890 )

• gene expression profiling indicates progressive neuroinflammation

abnormal forebrain morphology ( J:219890 )

• progressive forebrain weight loss at 6-10 months of age, with a 34% forebrain weight loss at 10 months of age

abnormal medium spiny neuron morphology ( J:219890 )

• about 40% loss of striatal medium spiny neurons at 10 months of age

decreased striatum size ( J:219890 )

• striatal volume loss in 10 month old mice

abnormal cerebral cortex morphology ( J:219890 )

• cortical volume loss in 10 month old mice

brain atrophy ( J:219890 )

astrocytosis ( J:219890 )

• reactive astrocytes with hypertrophic processes are seen in the striatum and cortex at 10 months of age

neuronal intranuclear inclusions ( J:219890 )

• nuclear inclusions containing aggregated mutant HTT are seen in both the cortex and striatum by 6 months of age and in other brain regions such as the hippocampus, thalamus, cerebellum, and brain stem at 6-10 months of age

• however, cytoplasmic aggregates are not seen

neurodegeneration ( J:219890 )

abnormal nervous system electrophysiology ( J:219890 )

• local field potential recordings in the cortex and dorsal striatum show synchronous, short duration, large-amplitude events in the low gamma range in 7-9 month old mice

• differences in gamma frequency events are already seen in 16-18 week old mice and progressively worsen with age

• however, epileptic activity is not seen is cortical local field potential recording

reproductive system

testicular atrophy ( J:219890 )

♂ • in 10 month old mice

male infertility ( J:219890 )

♂ • age-dependent infertility starting around 5 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:219890