A mutant human JPH3 gene containing 116 CTG/CAG repeats in exon 2A is expressed in these mice. By 6 months of age they display neurodegeneration accompanied by a progressive motor deficit. Thes mice may have useful applications in the study of the polyglutamine (polyQ) neurodegenerative disease, Huntington's disease-like-2 (HDL2).
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) |
The autosomal dominant neurodegenerative disorder Huntington's disease-like-2 (HDL2) is caused by a CTG/CAG repeat expansion in exon 2A of the junctophilin 3 (JPH3) gene. A mutant human JPH3 gene containing 116 CTG/CAG repeats in exon 2A is expressed in these mice. Transgene mRNA expression is detected in brain by RT-PCR analysis and is approximately 2 fold greater than endogenous mouse Jph3 expression. Mutant protein levels are not significantly overexpressed. Transgenic mice exhibit progressive motor deficits by 6 months of age. At 3 months of age, no motor deficits are detected. By 12 months of age, transgenic mice have reduced forebrain weight and cortical volume. Ubiquitin-positive nuclear inclusions are detected in transgenic mice as early as 3 months of age in the the cortex and hippocampus. By 12 months of age, nuclear inclusions are detected in a pattern similar to that seen in human patients: upper cortical layers, hippocampus, amygdala, as well as in the cerebral cortex and striatum. Poly(CUG) RNA foci that colocalize with MBNL1 are detected in cortical sections from 6 month old transgenic mice. Mice hemizygous for the transgenic insert are viable, fertile, and normal in size. The Donating Investigator has not attempted to make the strain homozygous.
The human bacterial artificial chromosome (BAC) RP11-33A21 containing the entire JPH3 gene, and approximately 30kb 5' and 40kb 3' genomic flanking sequence, was modified by inserting 120 CTG/CAG repeats in exon 2A. The transgenic construct was microinjected into the pronucleus of FVB/N fertilized eggs. Founder line C line, which has 116 CTG/CAG repeats, was subsequently established. 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 | JPH3, junctophilin 3, human |
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Site of Expression |
Allele Name | transgene insertion C, X William Yang |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | BAC-HDL2 |
Gene Symbol and Name | Tg(JPH3*)CXwy, transgene insertion C, X William Yang |
Gene Synonym(s) | |
Promoter | JPH3, junctophilin 3, human |
Expressed Gene | JPH3, junctophilin 3, human |
Strain of Origin | FVB/N |
Chromosome | UN |
Molecular Note | The human BAC (RP11-33A21) was modified to include an expanded CTG/CAG track of 120 repeats in exon 2A of JPH3. This line has a single integration of the transgene with 116 CTG/CAG repeats. RT-PCR analysis indicates the level of overexpression of the transgene was about 100% of the endogenous gene. |
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.
When using the BAC-HDL2 mouse strain in a publication, please cite the originating article(s) and include JAX stock #017483 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Hemizygous or Non carrier for Tg(JPH3*)CXwy |
Frozen Mouse Embryo | FVB-Tg(JPH3*)CXwy/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | FVB-Tg(JPH3*)CXwy/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | FVB-Tg(JPH3*)CXwy/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | FVB-Tg(JPH3*)CXwy/J Frozen Embryo | $3373.50 |
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