These prion protein-deficient mice are resistant to prion disease and serve as a PrP-deficient background for mouse models of spongiform encephalopathies and neurologic prion disorders.
Stanley Prusiner, University of California, San Francisco
A neo cassette replaces part of exon 3 of the prion protein (Prnp) gene in this strain, abolishing gene function. Prnp encodes the glycoprotein PrPC which is attached to the external surface of central nervous system (CNS) neurons by a glycosylphosphatidyl inositol (GPI) anchor. Conformational changes in PrPC to an infectious form, PrPSc, either by exogenous introduction or as a result of spontaneous mutation, have been linked to the development of spongiform encephalopathies such as scrapie in sheep and Creutzfeld-Jakob disease or GerstmannStraussler-Scheinker syndrome in man. These PrP0/0 mice are viable and fertile. They exhibit decreased copper levels in the brain, impaired synaptic transmission, defective sleep-wake cycles, and altered circadian rhythms. When inoculated with PrPSc, PrP0/0 mice are resistant to prion disease and do not replicate the infectious proteins. These mice serve as a PrPC-deficient background for transgenic mice expressing GPI anchor defects (see (Stock No. 018124).
A targeting vector was designed to replace part of exon 3 of the prion protein (Prnp) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S7/SvEvBrd-Hprt+-derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6J females. These Prnp0/0 mice were backcrossed to C57BL/6J mice and subsequently to FVB/NCrl mice for 10 generations. Zygotes from these mice were microinjected with a transgene expressing PRNP lacking the GPI anchor signal (Tg(Prnp-tTA)F959Sbp). Upon arrival at The Jackson Laboratory, Tg959/Prnp0/0 mice were bred to FVB/NJ (Stock No. 001800) for at least one generation. The Tg(Prnp-tTA)F959Sbp transgene was bred out and discarded. A colony of mice containing only the Prnp0/0 allele was established.
Of note, another mouse line containing the Tg(Prnp-tTA)F959Sbp allele was imported and is maintained as Stock No. 018124.
|Allele Name||targeted mutation 1, Charles Weissmann|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Prnptm1Cwe; targeted mutation 1, Charles Weissmann|
|Gene Symbol and Name||Prnp, prion protein|
|Gene Synonym(s)||PrPSc; AI325101; AltPrP; prion protein, structural locus; Sinc; CD230; GSS; AA960666; Sinc; Prn-i; Prn-p; PrP27-30; PrP33-35C; PrPC; PRIP; Prn-i; Prn-p; PrP; ASCR; expressed sequence AA960666; p27-30; expressed sequence AI325101; CJD; KURU; prion protein, scrapie incubation time regulation; scrapie incubation period; Prn; PrPc|
|Strain of Origin||129S7/SvEvBrd-Hprt+|
|Molecular Note||A 552 bp fragment of the coding region contained within exon 3 was replaced with a 1.1 kb cassette containing the TK promoter followed by the neomycin gene.|
|Mutations Made By|| |
Stanley Prusiner, University of California, San Francisco
When maintaining a live colony, homozygous mice may be bred together.
When using the FVB.129S7(B6)-Prnptm1Cwe/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #018122 in your Materials and Methods section.
|Heterozygous for Prnp<tm1Cwe>|
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