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Development of mouse models for the study of bovine transmissible spongiform encephalopathy - SE1416

Description
• The work addresses policy issues related to the development of sensitive, rapid and validated models for the detection and characterisation of BSE.
• Transgenic mice in which the mouse PrP gene has been replaced with the bovine PrP gene will be produced to study the susceptibility of cows to scrapie and BSE isolates.
• Gene targeting techniques will be used to replace the coding region of the endogenous murine PrP gene for that of the bovine PrP gene.
• Two different bovine genes constructs will be used for the targeting experiment coding for 5 or 6 octapeptide repeats.
• Targeting constructs will be electroporated into the HMI murine embryonic stem cell line.
• Targeted clones will be identified by selection in thioguanine and confirmed by PCR and genomic Southern analysis.
• Clones in which one copy of the murine gene has been replaced by the bovine gene will be injected into blastocysts and reimplanted into foster mothers for the production of chimaeric mice.
• The chimaeras will be bred to produce mice homozygous for the introduced bovine PrP genes.
• The two different lines of mice will be crossed to produce mice with all three genotypes of the bovine PrP genes.
• The transgenic mice will be validated as a model for bovine TSEs by infection with scrapie and BSE isolates,
Project Documents
• Final Report : Final report   (115k)
Time-Scale and Cost
From: 1996

To: 2001

Cost: £530,233
Contractor / Funded Organisations
Institute for Animal Health (BBSRC)
Keywords
Animal Health              
Bio-assay              
Biotechnology              
BSE              
Plants and Animals              
Transgenic              
Transmission              
TSEs              
Fields of Study
Animal Health