FVB/NJ-Tg(YAC72)2511Hay/J

Stock number: 003640
Product name: YAC72

Description

These YAC72 mice express a transgene containing human Huntingtin protein and develop functional, behavioral, and pathological changes similar to those of patients with Huntington's Disease.

Detailed description

Mice homozygous for this transgene are viable and fertile. The human huntingtin transgenic protein is expressed widely in many tissues (identical to the endogenous huntingtin protein), but has highest levels of expression in the brain and testes. Electrophysiological abnormalities can be measured by six months. A behavioral phenotype is first detected at seven months when evidence of mild hyperkinetic movement disorder is noticeable. This disorder is characterized by progressive spontaneous hyperactivity during the dark phase of open field-testing. By 12 months of age selective degeneration of medium spiny neurons in the lateral striatum is observed. This degeneration is associated with the translocation of N-terminal huntingtin fragments to the nucleus. This strain represents a Huntington's Disease mouse model where a mutant full-length human huntingtin is expressed under control of its endogenous promoter.

Development

A YAC containing a full-length human huntingtin gene was modified with a 72 CAG repeat expansion in exon 1. The resulting construct (YAC72) was injected into FVB/N pronuclei.

Allele

Symbol: Tg(YAC72)2511Hay
Name: transgene insertion 2511, Michael Hayden
MGI accession ID: MGI:2429756
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(YAC72)2511Hay
Marker name: transgene insertion 2511, Michael Hayden
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: HTT,huntingtin,human
Molecular note: A YAC containing a full-length human huntingtin gene was modified with a 72 CAG repeat expansion in exon 1. The resulting construct (YAC72) was used to generate transgenic mice. The endogenous human HDH promoter directed expression in many tissues with levels in the brain and testes being the highest.
General note: Homozygous transgenic mice are viable and fertile. In these mice the human huntingtin transgenic protein is expressed widely in many tissues (identical to the endogenous huntingtin protein), with highest expression levels in the brain and testes. Electrophysiological abnormalities can be measured by 6 months. A behavioral phenotype is first detected at 7 months when evidence of mild hyperkinetic movement disorder is noticeable. This disorder is characterized by progressive spontaneous hyperactivity during the dark phase of open field-testing. By 12 months of age selective degeneration of medium spiny neurons in the lateral striatum is observed. This degeneration is associated with the translocation of N-terminal huntingtin fragments to the nucleus.