FVB/N-Tg(YAC353G6)W7Hay/J

Stock number: 007247
Product name: C6R7
Research areas: Neurobiology Research

Description

These transgenic mice express the human huntingtin protein with a mutation conferring resistance to caspase-6 cleavage to the gene product. Delayed nuclear localization of mutant huntingtin protein in brains of these transgenic mice is seen at nine months of age, but an increase of nuclear huntingtin is observed by 12 months of age.

Detailed description

These transgenic mice express the human huntingtin protein containing a 133 CAG repeat expansion and a mutation in exon 13 conferring resistance to caspase-6 cleavage to the gene product.

Expected caspase-6 cleaved fragments are not detected in brain lysates by Western blot analysis. Transgenic mice have brain weight and striatal volume similar to wild-type controls and do not exhibit neuronal loss at 12 months of age when compared to transgenic mice that express human huntingtin protein containing a 128 CAG repeat (FVB-Tg(YAC128)53Hay/J Stock No. 004938). These transgenic mice have activity levels and motor function similar to wild-type controls, and are resistant to neuron excitotoxicity. Immunohistochemical analysis of striatal brain sections reveals delayed nuclear localization of mutant huntingtin protein in these transgenic mice at nine months of age. Between nine and 12 months of age, an increase of nuclear huntingtin is observed. Homozygotes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

This mutant mouse strain represents a model that may be useful in studies of Huntington's disease. This strain can serve as the control for the FVB-Tg(YAC128)53Hay/J (Stock No. 004938).

Development

A YAC containing a full-length human huntingtin gene was modified with a 133 CAG repeat expansion in exon 1 and a mutation in exon 13, at position 586, which encodes the caspase-6 cleavage site. The resulting construct (YAC353G6) was injected into FVB/NJ pronuclei. Founder line W7 (C6R7) was subsequently established. The mice were then backcrossed to FVB/NJ for 17 generations before arriving at The Jackson Laboratory.

Allele

Symbol: Tg(YAC353G6)W7Hay
Name: transgene insertion W7, Michael Hayden
MGI accession ID: MGI:3710982
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(YAC353G6)W7Hay
Marker name: transgene insertion W7, Michael Hayden
Chromosome: UN
Strain of origin: FVB/NJ
Expressed genes: HTT,huntingtin,human
Molecular note: A YAC containing a full-length human huntingtin gene was modified with a 133 CAG repeat expansion in exon 1 and a mutation in exon 13, at position 586, which encodes the caspase-6 cleavage site. Founder line W7 (C6R7) was subsequently established. Caspase-6 cleavage products are not detected in brain lysates by Western blot.