FVB.129S7(B6)-Prnp^tm1Cwe/J

Stock number: 018122
Research areas: Cell Biology Research, Mouse/Human Gene Homologs

Description

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.

Detailed description

A neo cassette replaces part of exon 3 of the prion protein (Prnp) gene in this strain, abolishing gene function. Prnp encodes the glycoprotein PrP^C which is attached to the external surface of central nervous system (CNS) neurons by a glycosylphosphatidyl inositol (GPI) anchor. Conformational changes in PrP^C to an infectious form, PrP^Sc, 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 PrP^0/0 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 PrP^Sc, PrP^0/0 mice are resistant to prion disease and do not replicate the infectious proteins. These mice serve as a PrP^C-deficient background for transgenic mice expressing GPI anchor defects (see (Stock No. 018124).

Development

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 Prnp^0/0 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/Prnp^0/0 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 Prnp^0/0 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

Symbol: Prnp^tm1Cwe
Name: targeted mutation 1, Charles Weissmann
MGI accession ID: MGI:1888773
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Prnp trn^1Zrch; Prnp^-; Prnp⁰; Prn-p⁰; Prnp⁰ Zurich I; Prnp^tm1ZH1; Prnp^tm1Zrch; PrnpZH1; PrP⁰; PrP^C Zrch-1; PrP^C-KO; Zrch 1 Prnp⁰; Zrch Prnp⁰; ZrchI Prnp-; Zurich line
Marker symbol: Prnp
Marker name: prion protein
Marker synonyms: AltPrP; ASCR; CD230; CJD; GSS; KURU; p27-30; PRIP; Prn; Prn-i; Prn-p; PrP; PrP27-30; PrP33-35C; PrPc; PrPSc; Sinc
Chromosome: 2
Strain of origin: 129S7/SvEvBrd-Hprt1⁺
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.