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| These BACHD transgenic mice express a neuropathogenic, full-length human mutant Huntingtin (fl-mhtt) gene modified to harbor a loxP-flanked human mutant htt exon 1 sequence (containing 97 mixed CAA-CAG repeats encoding a continuous polyglutamine (polyQ) stretch). These mice may be useful in the testing of candidate therapeutics and in studies examining the contribution of mhtt expression in individual neuronal and non-neuronal cell types in the pathogenesis of HD-like phenotypes in vivo. | |||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System Heterozygote x +/+ sibling (Female x Male) Species laboratory mouse Donating Investigator X. William Yang, University of California Los Angeles Description
Mice hemizygous for the BACHD transgene are viable and fertile. Under the control of endogenous human htt regulatory machinery, BACHD mice have relatively high expression levels of a neuropathogenic, full-length human mutant Huntingtin (fl-mhtt) modified to harbor a loxP-flanked human mutant htt exon 1 sequence (containing 97 mixed CAA-CAG repeats encoding a continuous polyglutamine (polyQ) stretch). Prior to Cre recombinase exposure, BACHD mice exhibit progressive motor deficits, neuronal synaptic dysfunction, and selective late-onset neuropathology without somatic polyQ repeat instability in the aged brain. Moreover, BACHD mice reproduce a mhtt aggregation pattern reminiscent of that in adult-onset Huntington's disease (HD). Importantly, a relatively steady-state level of predominantly fl-mhtt and a small amount of mhtt N-terminal fragments present in both the nucleus and cytoplasm, are responsible for the onset and progression of neuropathology. Upon exposure to Cre recombinase, the floxed mhtt-exon1 portion of the transgene is removed and fl-mhtt expression is terminated. These BACHD mice represent a robust in vivo paradigm for studying the HD pathogenesis elicited by fl-mhtt. These mice may be useful in the testing of candidate therapeutics and in studies examining the contribution of mhtt expression in individual neuronal and non-neuronal cell types in the pathogenesis of HD-like phenotypes in vivo.Development
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). DNA from a modified BAC clone was used as the source for the BACHD transgene and microinjected into FVB fertilized eggs. Mice from founder line BACHD-I were found to express relatively high levels of full-length human mutant Huntingtin (fl-mhtt) and harbor tandem integrates of approximately 5 copies of the transgene. These BACHD-I transgenic mice were subsequently maintained on the FVB/NJ genetic background for many generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to FVB/NJ inbred mice for at least one generation to establish the colony.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of HTT
006471 B6.Cg-Tg(HDexon1)61Gpb/J 004360 B6;SJL-Tg(HD)63Aron/J 003627 B6C3-Tg(HD82Gln)81Dbo/J 002809 B6CBA-Tg(HDexon1)61Gpb/1J 002810 B6CBA-Tg(HDexon1)62Gpb/1J 006494 B6CBA-Tg(HDexon1)62Gpb/3J 007578 CBy.Cg-Tg(HDexon1)61Gpb/J 004938 FVB-Tg(YAC128)53Hay/J 007247 FVB/N-Tg(YAC353G6)W7Hay/J 003640 FVB/NJ-Tg(YAC72)2511Hay/J View Strains carrying other alleles of HTT (10 strains)
Additional Web Information
Cre-lox Systems
Phenotype
Phenotype Information
assigned by genotype
Tg(HTT*97Q)IXwy/0
FVB-Tg(HTT*97Q)IXwy
- growth/size phenotype
- weight gain (MGI Ref ID J:137345)
- mice show significant weight gain of 20-30% over control weights in the 2-12 month period of testing
- behavior/neurological phenotype
- impaired coordination (MGI Ref ID J:137345)
- at 2, 6 and 12 months, transgenics display decline in performance in rotating rod tests, compared to wild-type controls; performance declines with increasing age in mutants, but age has no effect in controls
- nervous system phenotype
- abnormal brain morphology (MGI Ref ID J:137345)
- at 6 months of age, brains do not display any obvious pathology, but at 12 months, brains are visibly atrophic compared to wild-type
- abnormal cerebral cortex morphology (MGI Ref ID J:137345)
- at 12 months, robust decrease in cerebral cortex volume (32% of wild-type) is observed
- abnormal striatum morphology (MGI Ref ID J:137345)
- at 12 months, robust decrease in striatal volume (28% of wild-type) is observed
- decreased brain weight (MGI Ref ID J:137345)
- at 12 months, forebrain weight (whole brain minus cerebellum and olfactory bulb) is 20% lower than wild-type controls; however cerebellar weight is comparable
- abnormal nervous system electrophysiology (MGI Ref ID J:137345)
- medium and large amplitude spontaneous currents in medium spiny neurons (MSNs) are reduced compared to wild-type, while probability of occurrence of small amplitude events is significantly elevated
- neurodegeneration (MGI Ref ID J:137345)
- evident at 12 months in transgenic mice, but not in wild-type
- neuron degeneration (MGI Ref ID J:137345)
- striatal neuron degeneration is observed at 12 months, but not in wild-type brains
- neuronal intranuclear inclusions (MGI Ref ID J:137345)
- at 12 and 18 months, large mutant huntingtin (mhtt) protein inclusions are detected in deep cortical layers with smaller inclusions found in the upper cortical layers with very few small inclusions in striatal neurons
This mouse can be used to support research in many areas including:
HTT relatedMouse/Human Gene Homologs
Huntington's disease (chorea)
Neurobiology Research
Behavioral and Learning Defects
Cre-lox System (loxP-flanked Sequences)
Huntington's disease
Research Tools
Cre-lox System (loxP-flanked Sequences)
Developmental Biology Research
Neurodevelopmental Defects
Mouse/Human Gene Homologs
Huntington's disease (chorea)
Neurobiology Research
Ataxia (Movement) Defects
Behavioral and Learning Defects
Cortical Defects
Huntington's disease
Neurodegeneration
Neurodevelopmental Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects
Tremor Defects
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(HTT*97Q)IXwy | ||
|---|---|---|---|
| Allele Name | transgene insertion I, X William Yang | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | BACHD-I; | ||
| Mutation Made By | X. William Yang, University of California Los Angeles | ||
| Strain of Origin | FVB | ||
| Expressed Gene | HTT, huntingtin, human | ||
| Promoter | HTT, huntingtin, human | ||
| 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). DNA from a modified BAC clone was used as the source for the BACHD transgene and microinjected into FVB fertilized eggs. Mice from founder line BACHD-I were found to express relatively high levels of full-length human mutant Huntingtin (fl-mhtt) in the brain by qRT-PCR and the mice harbor tandem integrates of approximately 5 copies of the transgene. Another line, named BACHD-L, was analyzed, showing that the phenotypic aspects of line I were replicated in this strain. [MGI Ref ID J:137345] | ||
Genotyping
Genotyping Information
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Gray M; Shirasaki DI; Cepeda C; Andre VM; Wilburn B; Lu XH; Tao J; Yamazaki I; Li SH; Sun YE; Li XJ; Levine MS; Yang XW. 2008. Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice. J Neurosci 28(24):6182-95. [PubMed: 18550760] [MGI Ref ID J:137345]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygous mice may be bred to wildtype siblings or to FVB/NJ inbred mice. Mating System Heterozygote x +/+ sibling (Female x Male)
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.
Estimated Available for Sale Date:
Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.
View All Strains Under Development and On Hold
Supply Details
| Standard Supply | Under Development for Distribution Colony |
|---|---|
| Supply Notes |
|
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
General Terms and Conditions
See Terms of Use
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.Ordering and Purchasing Information
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Terms of Use
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General Terms and Conditions
Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.
For additional Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.
Contact information
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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