B6;SJL-Tg(HD)63Aron/J

Stock number: 004360
Product name: HD100

Description

These HD100 mice express a transgene containing the initial N-terminal third of the mutant human huntingtin gene (IT15), and exhibit increased levels of nuclear and cytoplasmic huntingtin and dysmorphic dendrites in the striatum and cortex.

Detailed description

These transgenic mice express the initial N-terminal third of the mutant human huntingtin gene (IT15) under the direction of the rat neuron-specific enolase promoter. Expected transgene expression was confirmed by Northern blot, RT-PCR and Western blot analysis. Mice heterozygous for the transgene have a phenotype mimicking much of the morphological and subcellular neuropathology that occurs in the striatum and cortex in human Huntington's disease. Behavioral abnormalities are varible in onset and intensity, beginning between three to six months of age. Transgenic mice exhibit increased levels of nuclear and cytoplasmic huntingtin and dysmorphic dendrites in the striatum and cortex. Electron microscopic analysis of nuclear inclusions of cortical and striatal neurons detects granular and filamentous structures that appear to be similar to structures seen in brain affected by Huntington's disease. Cortical stimulation and N-methyl-D-aspartate (NMDA) receptor activation produces abnormal electrophysiological responses from striatal neurons.

Development

A transgenic construct containing bases 316-3210 of the human huntingtin cDNA sequence with a 100 CAG repeat insertion under the control of the rat neuron-specific enolase promoter and an SV40 polyadenylation signal, was introduced into oocyte pronuclei from C57BL/6 X SJL F1 hybrid mice. Transgenic mice were bred to B6;SJL mice.

Allele

Symbol: Tg(HD)63Aron
Name: transgene insertion 63, Neil Aronin
MGI accession ID: MGI:3057174
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(HD)63Aron
Marker name: transgene insertion 63, Neil Aronin
Chromosome: UN
Strain of origin: (C57BL/6 x SJL)F1
Expressed genes: HTT,huntingtin,human
Molecular note: The transgene contains bases 316-3210 of the human huntingtin cDNA sequence with a 100 CAG repeat insertion, under the control of the rat neuron-specific enolase promoter and an SV40 polyadenylation signal. Northern blot, RT-PCR, and Western blot analyses detected expression in neural cells.
General note: Transgenic mice express the initial N-terminal third of the mutant human huntingtin gene (IT15) under the direction of the rat neuron-specific enolase promoter. The phenotype of hemizygous transgenic mice mimicks much of the morphological and subcellular neuropathology that occurs in the striatum and cortex in the human Huntington disease. Onset and intensity of behavioral abnormalities are variable and begin between 3 to 6 months of age.

Transgenic mice exhibit increased levels of nuclear and cytoplasmic huntingtin and dysmorphic dendrites in the striatum and cortex. Electron microscopic analysis of nuclear inclusions of cortical and striatal neurons detects granular and filamentous structures that appear to be similar to structures seen in human brain affected by Huntington's disease. Cortical stimulation and N-methyl-D-aspartate (NMDA) receptor activation produce abnormal electrophysiological responses from striatal neurons of transgenic mice.