Overview

Also Known As: FVB.BAC HD ; BACHD on FVB/NJ back ground ; CHDI-81001011

The FVB/N-congenic BAC HD transgenic line L expresses multiple copies of a transgene encoding the full-length human huntingtin gene (HTT; HD or Hdh) modified to have a floxed exon 1 containing 97 mixed CAA-CAG repeats. These FVB.BAC HD (or FVB.BACHD-L) mice may be useful for studying Huntington's disease on a defined congenic background, as well as for exploring the effect of interrupted CAG tracts versus non-interrupted CAG tracts on somatic instability and RNA structure mechanisms in HD pathophysiology.

Donating Investigator

X. William Yang, University of California Los Angeles

Dr. David Howland, CHDI Foundation

Genetic overview

Genetic Background	Generation

Tg(HTT*97Q)LXwy

Allele Type
Transgenic (Conditional ready (e.g. floxed), Inserted expressed sequence, Humanized sequence)

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Research Applications

Neurobiology Research
Research Tools
Mouse/Human Gene Homologs

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Stock No. 027433 was formerly associated with CHDI Foundation colony Stock No. 370192 [CHDI-81001011].

Huntington's disease (HD) is an autosomally dominant, fatal neurodegenerative disorder characterized by uncontrolled movements, psychiatric disturbances and cognitive impairment. HD is caused by an unstable trinucleotide (polyglutamine) repeat expansion in the huntingtin gene (HTT; HD or Hdh).

The BAC HD transgenic mouse line L expresses multiple copies of full-length human HTT with a mutant exon 1 containing a 97 glutamine repeat tract (mixed CAG-CAA repeats) at levels 1.5 to 2 times higher than the endogenous mouse Htt; a function of higher numbers of transgene copies inserted. Of note, the mutant exon 1 is flaked with loxP sites.

Stock No. 027433: The FVB/N-congenic BAC HD transgenic mouse line L is called FVB.BAC HD or FVB.BACHD-L. Hemizygous mice are viable, fertile and normal in size. Hemizygous mice are viable and fertile, with activity defects (hyperactivity in ~8 week old females but hyperactivity by 8 weeks [mainly in females)), abnormal gait, and motor impairment (rotarod deficit ~4 weeks of age). These mice exhibit weight gain (which can confound motor endpoint evaluation) evident in both sexes from ~4 weeks of age. Overall survival is similar to wildtype (noncarrier) mice up to 1 year of age or longer. The FVB.BACHD-L mice are not further characterized to date (April 2014).

While genetic background may lead to variations in disease severity/progression, these FVB.BACHD-L mice may exhibit a phenotype similar to that of BAC HD mice from the same founder line with less backcrossing onto the FVB/N genetic background (described and available as Stock No. 017487. Briefly, mutant HTT protein is detected in cortex, striatum, and cerebellum by Western blot analysis. qPCR results indicated that there are tandem integrations of approximately 5 copies of the transgene. The 97 CAA-CAG repeat length is stable in maternal and paternal germline transmission, as well as in brain tissue from 12 month old transgenic mice. Onset of progressive motor deficits is 2 months of age. Transgenic mice weigh 8-14% more than wildtype controls. In transgenic mice 12 months of age, a few mutant HTT protein aggregates are observed in the cortical neuropil, with tiny aggregates in the striatum, which is similar to the pattern seen in adult onset Huntington's Disease.

Importantly, if a behavioral testing battery includes cognitive tests that require the animals to use visual cues, the C57BL/6 genetic background mice may be preferred as the FVB/N genetic background imparts the Pde6b^rd1 mutation causing retinal degeneration and blindness at an early age. In addition, the relatively high aggression levels in FVB/N mice, especially males, may cause problems during experiments that require long-term group-housing. Conversely, mice on the C57BL/6-congenic background may exhibit age-related hearing loss and become deaf to certain frequencies.

This Huntington's disease mouse model is available by way of a collaborative effort between CHDI Foundation, Dr. X. William Yang (University of California, Los Angeles) and The Jackson Laboratory.

Development

The BAC HD transgene was designed by Dr. X. William Yang (University of California, Los Angeles).
The 240 kbp human bacterial artificial chromosome (BAC) RP11-866L6 containing the entire 170 kbp human HTT gene, and approximately 20 kbp of 5' and 50 kbp of 3' flanking sequences, was modified by replacing exon 1 with a loxP-flanked fragment containing 97 mixed CAA-CAG repeats. The transgenic construct was microinjected into the pronucleus of FVB/N fertilized eggs. Founder line L was subsequently established and maintained on the FVB/NJ background. BAC HD mice were sent to the CHDI Foundation colony, where they were backcrossed with FVB/N inbred mice for several generations to create the FVB/N-congenic colony (FVB.BAC HD or FVB.BACHD-L), called CHDI Foundation colony Stock No. 370192 [CHDI-81001011]. In 2015, FVB.BAC HD animals from backcross generation N21-N22 were sent from the CHDI Foundation colony to The Jackson Laboratory Repository, from which FVB.BAC HD hemizygous mice are available as Stock No. 027433.

Expression Data

Expressed Gene	HTT, huntingtin, human
Site of Expression

Control Suggestions

Noncarrier
001800 FVB/NJ

Additional Information

Considerations for Choosing Controls

Selected References

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):6182-95PubMed: 18550760 MGI: J:137345

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Genetics

Tg(HTT*97Q)LXwy

Allele Symbol: Tg(HTT*97Q)LXwy

Allele Name	transgene insertion L, X William Yang
Allele Type	Transgenic (Conditional ready (e.g. floxed), Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	Tg(HTT*97Q)LXwy; transgene insertion L, X William Yang
Gene Symbol and Name	Tg(HTT*97Q)LXwy, transgene insertion L, X William Yang
Gene Synonym(s)	BACHD-L
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). Two lines were created (line I and L) that exhibit the same phenotype.
Mutations Made By	X. William Yang, University of California Los Angeles

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Neurobiology Research
- Neurodegeneration
- Neuromuscular defects
- Ataxia (Movement) Defects
- Huntington's disease
- Behavioral and Learning Defects
Research Tools
- Neurobiology Research
Mouse/Human Gene Homologs
- Huntington's disease (chorea)

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Tg(HTT97Q)LXwy/0
FVB-Tg(HTT97Q)LXwy

behavior/neurological phenotype

impaired coordination
- starting at 2 months and worsening with age

growth/size/body region phenotype

increased body weight
- mice exhibit the same phenotype as Tg(HTT*97Q)IXwy mice

nervous system phenotype

abnormal brain morphology
- mice exhibit the same phenotype as Tg(HTT*97Q)IXwy mice

abnormal neuron morphology
- at 12 months, mice exhibit protein aggregates in the cortex and striatum unlike in wild-type mice

References

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):6182-95PubMed: 18550760 MGI: J:137345

Additional - Tg(HTT*97Q)LXwy related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR: Tg(HTT*97Q)IXwy repeat assay
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining our live colony, hemizygous mice are bred to FVB/NJ inbred mice (Stock No. 001800).
- Additional Breeding and Husbandry Support
Citation
When using the FVB.BAC HD ; BACHD on FVB/NJ back ground ; CHDI-81001011 mouse strain in a publication, please cite the originating article(s) and include JAX stock #027433 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Hemizygous or Non Carrier for Tg(HTT*97Q)LXwy

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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Also Known As: FVB.BAC HD ; BACHD on FVB/NJ back ground ; CHDI-81001011

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(HTT*97Q)LXwy

Allele Symbol: Tg(HTT*97Q)LXwy

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tg(HTT*97Q)LXwy/0FVB-Tg(HTT*97Q)LXwy

behavior/neurological phenotype

growth/size/body region phenotype

nervous system phenotype

References

Additional - Tg(HTT*97Q)LXwy related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Genotype: Tg(HTT97Q)LXwy/0
FVB-Tg(HTT97Q)LXwy