BAC SA transgenic mice express a mutant human HTT (huntingtin) gene that produces a protein that is phosphoresistant at the NT17 domain and has a 97 polyQ repeat expansion.
X. William Yang, University of California Los Angeles
Genetic Background | Generation |
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Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
These BAC SA transgenic mice express a mutant human HTT (huntingtin) gene containing nucleotide substitutions that result in amino acid substitutions of alanine for serine at positions 13 and 16, as well as a loxP-flanked fragment containing 97 mixed CAA-CAG repeats. The amino acid substitutions render the NT17 domain phosphoresistant (SA). Immunoprecipitation analysis confirmed that the mutant HTT protein is not phosphorylated. The mutant protein is expressed at a level higher than levels detected in the BACHD-L transgenic strain (STOCK No. 017487). At 2 months of age, BAC SA transgenic mice exhibit motor deficits, which progress with age. At 12 months of age, the mutant mice display decreased forebrain weight, anxiety and depression-like behavior and progressive protein aggregate formation in cortex and striatum. Mice that are hemizygous for the targeted mutation are viable, fertile and normal in size. The Donating Investigator has not attempted to make the strain homozygous.
When bred to Htt deficient mice, the transgene rescues the null embryonic lethal phenotype.
The 240 kb human bacterial artificial chromosome (BAC) RP11-866L6 containing the entire 170kb human HTT gene, and approximately 20 kbp of 5' and 50 kbp of 3' flanking sequences, was modified by nucleotide substitutions that result in amino acid substitutions of alanine for serine at positions 13 and 16, as well as replacing exon 1 with a loxP-flanked fragment containing 97 mixed CAA-CAG repeats. The SA transgenic construct was microinjected into the pronucleus of FVB/N fertilized eggs. Founder line 1 was subsequently established and maintained on the FVB/NJ background. Upon arrival at The Jackson Laboratory, the mice were crossed to FVB/NJ (Stock No. 001800) at least once to establish the colony.
Expressed Gene | HTT, huntingtin, human |
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Site of Expression |
Allele Name | transgene insertion 1, X William Yang |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | SA |
Gene Symbol and Name | Tg(HTT*)1Xwy, transgene insertion 1, X William Yang |
Gene Synonym(s) | |
Promoter | HTT, huntingtin, human |
Expressed Gene | HTT, huntingtin, human |
Strain of Origin | FVB |
Chromosome | UN |
Molecular Note | The 240 kb human bacterial artificial chromosome BAC(RP11-866L6), containing the entire 170 kb human Huntingtin (htt) genomic locus and approximately 20 kbp of 5' and 50 kbp of 3' flanking sequences, was modified by replacing the human htt exon 1 with a loxP-flanked human mutant htt exon 1 sequence (containing 97 mixed CAA-CAG repeats encoding a continuous polyglutamine (polyQ) stretch). Nucleotide substitution resulted in amino acid substitution of alanine for serine at positions 13 and 16. One line was created (no line number provided). |
Mutations Made By | X. William Yang, University of California Los Angeles |
When maintaining a live colony, these mice can be bred as hemizygotes. The Donating Investigator has not attempted to make the strain homozygous, but reports homozygotes should be viable.
When using the BAC SA mouse strain in a publication, please cite the originating article(s) and include JAX stock #017485 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Hemizygous or Non carrier for Tg(HTT*)1Xwy |
Frozen Mouse Embryo | FVB-Tg(HTT*)1Xwy/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | FVB-Tg(HTT*)1Xwy/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | FVB-Tg(HTT*)1Xwy/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | FVB-Tg(HTT*)1Xwy/J Frozen Embryo | $3373.50 |
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