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| These transgenic mice express a human TATA box binding protein, TBP, containing a 105 polyQ repeat expansion, under the control of the mouse prion protein promoter. Hemizygotes exhibit weight loss, kyphosis, locomotor impairment, nuclear inclusions of polyQ tracts in neurons, gliosis and neuron loss. This transgenic strain has a more severe phenotype and earlier onset of phenotype than B6CBA(FVB)-Tg(Prnp-TBP*)71-16Xjl/J (Stock No. 008216). B6CBA(FVB)-Tg(Prnp-TBP*)13Xjl/J (Stock No. 008083) can be used a control for this strain. This mutant mouse strain may be useful in studies of spinocerebellar ataxia 17 (SCA17) and polyglutamine (polyQ) related neurodegeneration. | |||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Mutant Stock; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System Hemizygote x F1 (Female x Male) HEMI x B6CBAF1 (100011) & recip only (not WT). Mating System F1 x Hemizygote (Female x Male) HEMI x B6CBAF1 (100011) & recip only (not WT). Species laboratory mouse Generation N11+ (16-JUN-08) Donating Investigator Xiao-Jiang Li, Emory University School of Medicine Description
These transgenic mice express a human TATA box binding protein, TBP, containing a 105 polyQ repeat expansion, under the control of the mouse prion protein promoter. The 105 polyQ-expansion is detected by Western blot analysis. At 3 months of age, hemizygous transgenic mice are smaller than wildtype littermates, appear ungroomed, exhibit kyphosis and weight loss. These transgenic mice have a shortened lifespan of 5 months and begin to die as early as 9 weeks of age. Immunohistochemical and Western blot analysis of brain tissue reveals neuronal nuclear aggregates of polyQ tracts by 8 weeks of age. Electron microscopic examination of brain tissue shows nuclear inclusions in cerebellar granule neurons and degeneration of Purkinje cells and axons. Reactive gliosis is observed in the granular and Purkinje layers. Loss of Purkinje cells is observed at 10 weeks of age. Apoptopic neurons in brain cortex and spinal cord are more abundant in transgenic mice when compared to wildtype. Early neurodegeneration is observed in the cerebral cortex. Onset of progressive locomotor impairment is 6 weeks of age. Some mice exhibit clasping, spontaneous seizures and tremors. The donating investigator has not attempted to make the strain homozygous. This transgenic strain has a more severe phenotype than B6CBA(FVB)-Tg(Prnp-TBP*)71-16Xjl/J (Stock No. 008216). B6CBA(FVB)-Tg(Prnp-TBP*)13Xjl/J (Stock No. 008083) can be used a control for this strain. This mutant mouse strain may be useful in studies of spinocerebellar ataxia 17 (SCA17) and polyglutamine (polyQ) related neurodegeneration.Development
A transgenic construct containing the human TATA box binding protein, TBP, containing a 105 polyQ repeat expansion, under the control of the mouse prion protein promoter was injected into fertilized FVB/N mouse eggs. Founder line TBP-105Q was established from a female animal. The founder female was bred to a FVB/NJ male. The mice were then crossed to B6CBAF1/J (Stock No. 100011) mice for 10 generations. The Donating Investigator reports that the strain did not thrive well enough to maintain on the FVB background.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 100011 B6CBAF1/J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Prnp
View Strains carrying other alleles of Prnp (20 strains)
008083 B6CBA(FVB)-Tg(Prnp-TBP*)13Xjl/J 008216 B6CBA(FVB)-Tg(Prnp-TBP*)71-16Xjl/J
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(Prnp-TBP*)105Xjl/0
FVB/N-Tg(Prnp-TBP*)105Xjl
- life span-post-weaning/aging
- premature death (MGI Ref ID J:130775)
- mice have reduced lifespans relative to wild-type; mice start to die as early as 9 weeks of age
- growth/size phenotype
- decreased body size (MGI Ref ID J:130775)
- symptomatic mice are visibly smaller than normal littermates at 3 months
- weight loss (MGI Ref ID J:130775)
- mice begin to lose body weight at 8 weeks of age
- behavior/neurological phenotype
- abnormal motor coordination/ balance (MGI Ref ID J:130775)
- onset of progressive motor impairment is 6 weeks of age
- impaired coordination (MGI Ref ID J:130775)
- mice perform poorly on a non-accelerating rotating rod at 6 weeks of age, and do not show any subsequent improvement
- limb grasping (MGI Ref ID J:130775)
- displayed by some mice
- poor grooming (MGI Ref ID J:130775)
- symptomatic mice can be distinguished from normal littermates at 3 months of age by poorly groomed appearance
- sporadic seizures (MGI Ref ID J:130775)
- some mice exhibit spontaneous seizures
- tremors (MGI Ref ID J:130775)
- displayed by some mice
- nervous system phenotype
- Purkinje cell degeneration (MGI Ref ID J:130775)
- degenerating Purkinje cells are evident in cerebellum
- abnormal neurite morphology (MGI Ref ID J:130775)
- loss or disruption of calbindin-positive neurites in cerebellar molecular layer is observed in mutants
- axon degeneration (MGI Ref ID J:130775)
- degenerating axons are evident in cerebellum; axons with reduced internal space surrounded by a distorted or thickened myelin sheath, presence of myelin ovoids, or vacuolated axons without distinguishable organelles or disintegrating myelin sheaths are indicative of more severe degeneration
- gliosis (MGI Ref ID J:130775)
- gliosis is observed in granular and Purkinje cell layers of cerebellum
- neuron degeneration (MGI Ref ID J:130775)
- degenerating neurons are detected in granular layer of cerebellum
- neuronal intranuclear inclusions (MGI Ref ID J:130775)
- prominent nuclear inclusions form in cerebellar granule neurons
- sporadic seizures (MGI Ref ID J:130775)
- some mice exhibit spontaneous seizures
- skeleton phenotype
- kyphosis (MGI Ref ID J:130775)
- posture is conspicuously abnormal in mutants; kyphosis, indicative of proximal muscle weakness, is observed by 3 months of age
This mouse can be used to support research in many areas including:
Neurobiology Research
Ataxia (Movement) Defects (Spinocerebellar ataxia)
Neurodegeneration
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(Prnp-TBP*)105Xjl | ||
|---|---|---|---|
| Allele Name | transgene insertion 105, Xiao-Jiang Li | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | TBP-105Q; | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | Tbp, TATA box binding protein, mouse, laboratory | ||
| Promoter | Prnp, prion protein, mouse, laboratory | ||
| Molecular Note | A transgenic construct containing the human TATA box binding protein, TBP, containing a 105 polyQ repeat expansion, under the control of the mouse prion protein promoter was injected into fertilized FVB/N mouse eggs. Founder line TBP-105Q was established. The 105 polyQ-expansion was detected in the cerebral cortex and cerebellum by Western blot analysis. [MGI Ref ID J:130775] | ||
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)
Friedman MJ; Shah AG; Fang ZH; Ward EG; Warren ST; Li S; Li XJ. 2007. Polyglutamine domain modulates the TBP-TFIIB interaction: implications for its normal function and neurodegeneration. Nat Neurosci 10(12):1519-28. [PubMed: 17994014] [MGI Ref ID J:130775]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry When maintaining a live colony on this F1 hybrid background, hemizygous mice are bred with B6CBAF1/J mice (Stock No. 100011). The Donating Investigator reports that the strain did not thrive well enough to maintain on the FVB background and bred male animals to female B6CBAF1/J mice. These TBP-105Q transgenic mice have a reduced lifespan of 5 months and begin to die as early as 9 weeks of age. Onset of progressive locomotor impairment is 6 weeks of age. The Donating Investigator has not attempted to make the strain homozygous. Mating System Hemizygote x F1 (Female x Male) HEMI x B6CBAF1 (100011) & recip only (not WT). F1 x Hemizygote (Female x Male) HEMI x B6CBAF1 (100011) & recip only (not WT). Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
This strain is currently This strain is currently on HOLD - Contact Customer Service for more information..
To register your interest in this strain go to the Strain Interest Form.
Estimated Available for Sale Date: 04-AUG-08
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
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $236.40 Female or Male Hemizygous for Tg(Prnp-TBP*)105Xjl *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $288.65 Hemizygous for Tg(Prnp-TBP*)105Xjl x Noncarrier $288.65 Noncarrier x Hemizygous for Tg(Prnp-TBP*)105Xjl
Additional Supply Details
| Supply Notes |
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $307.40 Female or Male Hemizygous for Tg(Prnp-TBP*)105Xjl *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $375.30 Hemizygous for Tg(Prnp-TBP*)105Xjl x Noncarrier $375.30 Noncarrier x Hemizygous for Tg(Prnp-TBP*)105Xjl
Additional Supply Details
| Supply Notes |
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Supply Details
| Standard Supply | This strain is currently on HOLD - Contact Customer Service for more information. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 100011 B6CBAF1/J | ||
| 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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Contact information
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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