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129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal
J C Manson1, A R Clarke, M L Hooper
1Institute for Animal Health, Edinburgh.
Abstract:
The neural membrane glycoprotein PrP is implicated in the pathogenesis of the transmissible spongiform encephalopathies; however, the normal function of PrP and its precise role in disease are not understood. Recently, gene targeting has been used to produce mice with neo/PrP fusion transcripts, but no detectable PrP protein in the brain (1). Here we report the use of a different targeting strategy, to produce inbred mice with a complete absence of both PrP protein and mRNA sequences. At 7 mo of age, these mice show no overt phenotypic abnormalities despite the normal high levels of expression of PrP during mouse development. The mice are being used in experiments designed to address the role of PrP in the pathogenesis of scrapie and the replication of infectivity.
Insights
Mice lacking prion protein (PrP) show no abnormalities, indicating PrP may not be essential for normal development. Further studies will explore PrP
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- The prion protein (PrP) is linked to transmissible spongiform encephalopathies.
- The normal function of PrP and its role in disease remain unclear.
Purpose of the Study:
- To create mice lacking both PrP protein and mRNA.
- To investigate the function of PrP in normal physiology and disease pathogenesis.
Main Methods:
- Gene targeting was employed to produce inbred mice with a complete absence of PrP.
- Phenotypic analysis was conducted on these PrP-null mice.
Main Results:
- Mice lacking PrP exhibited no overt phenotypic abnormalities at 7 months of age.
- This occurred despite the normal high expression of PrP during mouse development.
Conclusions:
- The absence of PrP does not cause apparent developmental defects in mice.
- These PrP-null mice provide a valuable model for studying scrapie pathogenesis and infectivity replication.