B6CBA(FVB)-Tg(Prnp-TBP*)71-16Xjl/J

Stock number: 008216
Research areas: Neurobiology Research

Description

These transgenic mice express a human TATA box binding protein, TBP, containing a 71 polyQ repeat expansion, under the control of the mouse prion protein promoter. Hemizygotes exhibit weight loss, locomotor impairment, gliosis and neuron loss. This transgenic strain has a less severe phenotype than B6CBA(FVB)-Tg(Prnp-TBP*)105Xjl/J (Stock No. 008075). 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.

Detailed description

These transgenic mice express human TATA box binding protein,TBP, containing a 71 polyQ repeat expansion, under the control of the mouse prion protein promoter. The 71 polyQ-expansion is detected by Western blot analysis. At 6.5 months of age, hemizygous transgenic mice are smaller than wildtype littermates and appear ungroomed. These transgenic mice have a shortened lifespan of approximately 9 months and begin to die as early as 21 weeks of age. Immunohistochemical and Western blot analysis reveals visible nuclear aggregates of polyQ tracts by 15 weeks of age. Electron microscopic examination of brain tissue shows degeneration of Purkinje cells and axons. Reactive gliosis is observed in the granular and Purkinje layers. Onset of progressive locomotor impairment is 7 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 less severe phenotype than B6CBA(FVB)-Tg(Prnp-TBP*)105Xjl/J (Stock No. 008075). 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 71 polyQ repeat expansion, under the control of the mouse prion protein promoter was injected into fertilized FVB/N mouse eggs. Founder line TBP-71Q-16 was established. Male animals were bred to FVB/NJ mice. 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.

Allele

Symbol: Tg(Prnp-TBP*)71-16Xjl
Name: transgene insertion 71-16, Xiao-Jiang Li
MGI accession ID: MGI:3772866
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: SCA17; TBP-71Q-16
Marker symbol: Tg(Prnp-TBP*)71-16Xjl
Marker name: transgene insertion 71-16, Xiao-Jiang Li
Marker synonyms: TBP-71Q-16
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: TBP,TATA-box binding protein,human
Molecular note: A transgenic construct containing the human TATA box binding protein, TBP, containing a 71 polyQ repeat expansion, under the control of the mouse prion protein promoter was injected into fertilized FVB/N mouse eggs. Founder line TBP-71Q-16 was established. The 71 polyQ-expansion is detected in the cerebral cortex and cerebellum by Western blot analysis.