Phenotypes Associated with This Genotype

Genotype
MGI:5698523

• Allelic Composition: Htt^tm2Detl/Htt⁺
• Genetic Background: B6J.129P2-Htt^tm2Detl

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

nervous system

microgliosis ( J:220868 )

♂ • mice with about 250 CAG repeats exhibit increased proliferation of microglia in the striatum

abnormal striatum morphology ( J:220868 )

♂ • mice with about 250 CAG repeats show a reduction in the striatum volume by 6 months of age but not at 3 months

♂ • striatal metabolites are altered by 9 months of age in mice with about 250 CAG repeats, with lower levels of N-acetylaspartate at 9 months, and lower levels of gamma-aminobutyric acid (GABA), glutamate, NAA, creatine + PCr and increased levels of glutamine and taurine at 12 months of age

decreased neocortex volume ( J:220868 )

♂ • mice with about 250 CAG repeats show a reduction in the neocortex volume by 6 months of age but not at 3 months

brain atrophy ( J:220868 )

♂ • mice backcrossed to C57BL/6J for 8 generations yields mice with about 250 CAG repeats which show acceleration of brain atrophy (striatum and neocortex) compared to mice with 150 or 200 CAG repeats that is most robust between 2 and 6 months of age

decreased oligodendrocyte number ( J:220868 )

♂ • mice with about 250 CAG repeats have decreased numbers of mature oligodendrocytes in the brain at P14

decreased myelin sheath thickness ( J:220868 )

♂ • mice with about 250 CAG repeats exhibit numerous smaller axons that are hypomyelinated with increased G-ratios (diameter of axon/outer diameter of the myelinaged fiber) in the corpus callosum at 12 months of age, indicating thinner myelin sheaths

neuronal intranuclear inclusions ( J:220868 )

♂ • mice with about 250 CAG repeats show nuclear progressive accumulation of mutant HTT aggregates from 6 to 12 months of age

abnormal oligodendrocyte physiology ( J:220868 )

♂ • mice with about 250 CAG repeats exhibit enhanced proliferation of oligodendrocyte precursor cells in the corpus callosum and striatum at 9 and 12 months of age

♂ • however, the number of oligodendrocyte precursor cells is normal

♂ • primary oligodendrocyte precursor cells from P6 mice with about 250 CAG repeats exhibit an extended S-phase

abnormal myelination ( J:220868 )

♂ • mice with about 250 CAG repeats show developmental delay of myelination, with lower levels of all isoforms of myelin basic protein and myelin oligodendrocyte glycoprotein in the striatum at P14

dysmyelination ( J:220868 )

♂ • mice with about 250 CAG repeats show fewer myelinated axons in the corpus callosum at P14

growth/size/body

weight loss ( J:220868 )

♂ • mice with about 250 CAG repeats exhibit lower body weight; they gain body weight normally up to 4 months, stop gaining weight and then lose weight

behavior/neurological

impaired coordination ( J:220868 )

♂ • mice with about 250 CAG repeats exhibit a motor deficit on the balance beam at 6 months of age, spending more time to cross the beam; motor deficits progress with age

hematopoietic system

microgliosis ( J:220868 )

♂ • mice with about 250 CAG repeats exhibit increased proliferation of microglia in the striatum

immune system

microgliosis ( J:220868 )

♂ • mice with about 250 CAG repeats exhibit increased proliferation of microglia in the striatum

homeostasis/metabolism

increased taurine level ( J:220868 )

♂ • mice with about 250 CAG repeats show increased levels of taurine in the striatum at 12 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:220868