Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation +pN1 Generation Definitions   Donating Investigator X. William Yang,   University of California Los Angeles

Description
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.

Development
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.

Control Information

	Control
	Noncarrier
	001800 FVB/NJ
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of JPH3

017484

FVB-Tg(JPH3-GFP,-JPH3*)GXwy/J

View Strains carrying other alleles of JPH3     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Huntington Disease-Like 2; HDL2

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Tg(JPH3*)CXwy/0

        involves: FVB/N

• nervous system phenotype
• abnormal forebrain morphology   (MGI Ref ID J:174267)
• • abnormal amygdala morphology
    • prominent ubiquitin immunoreactive inclusion bodies are detected at 12 months of age   (MGI Ref ID J:174267)
  • abnormal cerebral cortex morphology
    • reduction in cortical but not striatal volume with age   (MGI Ref ID J:174267)
    • prominent ubiquitin immunoreactive inclusion bodies are detected in the upper cortical layers at 12 months of age   (MGI Ref ID J:174267)
    • CUG RNA foci are detected in the cortex   (MGI Ref ID J:174267)
  • abnormal hippocampus morphology
    • prominent ubiquitin immunoreactive inclusion bodies are detected at 12 months of age   (MGI Ref ID J:174267)
  • abnormal striatum morphology
    • low levels of ubiquitin immunoreactive inclusion bodies are detected at 12 months of age   (MGI Ref ID J:174267)
• neurodegeneration
  • selective forebrain atrophy develops with age   (MGI Ref ID J:174267)
• neuronal intranuclear inclusions
  • prominent ubiquitin immunoreactive inclusion bodies are detected at 12 months of age   (MGI Ref ID J:174267)
  • inclusions are most abundant in the upper cortical layers, hippocampus, and amygdala with relatively low levels in the deep cortical layers and striatum   (MGI Ref ID J:174267)
  • inclusions can be detected as early as 3 months of age in the cortex and hippocampus   (MGI Ref ID J:174267)
• behavior/neurological phenotype
• impaired coordination
  • progressive motor deficits in a rotarod assay at 6 and 12 months of age, but not at 3 months of age   (MGI Ref ID J:174267)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Neurobiology Research
Huntington's disease
Neurodegeneration

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tg(JPH3*)CXwy
Allele Name		transgene insertion C, X William Yang
Allele Type		Transgenic (random, expressed)
Common Name(s)		BAC-HDL2;
Mutation Made By		X. William Yang,   University of California Los Angeles
Strain of Origin		FVB/N
Expressed Gene		JPH3, junctophilin 3, human
Promoter		JPH3, junctophilin 3, human
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. [MGI Ref ID J:174267]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(JPH3*)CXwy, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Wilburn B; Rudnicki DD; Zhao J; Weitz TM; Cheng Y; Gu X; Greiner E; Park CS; Wang N; Sopher BL; La Spada AR; Osmand A; Margolis RL; Sun YE; Yang XW. 2011. An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice. Neuron 70(3):427-40. [PubMed: 21555070]  [MGI Ref ID J:174267]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as hemizygotes. The Donating Investigator has not attempted to make the strain homozygous.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Noncarrier
	001800 FVB/NJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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