Phenotypes Associated with This Genotype

Genotype
MGI:3851446

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-HTT*94Q,-lacZ)1Rhn/0
• Genetic Background: involves: C57BL/6 * CBA

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

mortality/aging

premature death ( J:61490 )

• some mice die between 8 to 10 months due to injuries sustain from fighting with other mice

prenatal lethality, incomplete penetrance ( J:61490 )

• fewer than expected mice are recovered due to prenatal lethality

• however, treatment of pregnant dams with doxycycline eliminates prenatal lethality

nervous system

decreased brain size ( J:61490 )

enlarged brain ventricles ( J:61490 )

• ventricles are enlarged compared to in wild-type mice

abnormal dorsal striatum morphology ( J:61490 )

• the area of the caudate putamen is reduced compared to in wild-type mice

• however, treatment with doxycycline after the onset of symptoms restores some of the caudate putamen area

decreased striatum size ( J:61490 )

• the striatum is reduced in size compared to in wild-type mice

• the ventricular zone of the striatum is narrower than in wild-type mice

gliosis ( J:61490 )

• gliosis spreads throughout the lateral and medial striatum over time

astrocytosis ( J:61490 )

• mice exhibit reactive astrocytosis in the striatum that spreads over time

• however, treatment with doxycycline after the onset of symptoms reduces astrocytosis

neuronal intranuclear inclusions ( J:61490 )

• mice develop neuronal intranuclear and extranuclear inclusion

• however, treatment with doxycycline after the onset of symptoms alleviates inclusions

behavior/neurological

decreased grooming behavior ( J:61490 )

• in older mice with tremors

limb grasping ( J:61490 )

• beginning at 4 weeks, some mice exhibit limb grasping when suspended

• by 8 weeks, all mice display clasping that can last after mice are released

• however, treatment with doxycycline after the onset of symptoms reduces glasping behavior and duration

dystonia ( J:61490 )

• mice exhibit progressive motor dysfunction with choreic and dystonic movements, and parkinsonism

tremors ( J:61490 )

• mild tremors begin at 20 weeks in some mice

• in some mice tremors develop into a jerking motion

decreased locomotor activity ( J:61490 )

• at 36 weeks

muscle

dystonia ( J:61490 )

• mice exhibit progressive motor dysfunction with choreic and dystonic movements, and parkinsonism

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:61490