Home LiteratureArticle Details
PMID: 7999308 Published · ppublish English Journal Article

129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal.

Molecular neurobiology ·Vol. 8 ·No. 2-3 ·1994-00-00 ·Pages 121-7

Manson JC, Clarke AR, Hooper ML, Aitchison L, McConnell I, Hope J

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.

MeSH Terms
Aging/physiology Animals Blotting, Northern Brain/metabolism Chimera Embryo, Mammalian Gene Expression Genetic Vectors Heterozygote Homozygote Mice Mice, Inbred C57BL Mice, Inbred CBA Mice, Mutant Strains Mutation Prions/biosynthesis,genetics RNA, Messenger/biosynthesis Reference Values Scrapie/genetics,physiopathology
Chemicals
Prions RNA, Messenger
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Manson J C
Institute for Animal Health, Edinburgh.
Clarke A R
Hooper M L
Aitchison L
McConnell I
Hope J
References (34)
34 references, click to expand
  1. Genetic ablation of a mouse gene expressed specifically in brain.
    EMBO J. 1990 Feb;9(2):395-9 PMID: 2303033
  2. Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein.
    Nature. 1992 Apr 16;356(6370):577-82 PMID: 1373228
  3. New mutation in scrapie amyloid precursor gene (at codon 178) in Finnish Creutzfeldt-Jakob kindred.
    Lancet. 1991 Feb 16;337(8738):425 PMID: 1671440
  4. Use of BRL-conditioned medium in combination with feeder layers to isolate a diploid embryonal stem cell line.
    Roux Arch Dev Biol. 1989 May;198(1):48-56 PMID: 28305783
  5. Linkage of the scrapie-associated fibril protein (PrP) gene and Sinc using congenic mice and restriction fragment length polymorphism analysis.
    J Gen Virol. 1987 Oct;68 ( Pt 10):2711-6 PMID: 2889794
  6. Distinct prion proteins in short and long scrapie incubation period mice.
    Cell. 1987 Nov 20;51(4):651-62 PMID: 2890436
  7. Linkage of prion protein and scrapie incubation time genes.
    Cell. 1986 Aug 15;46(4):503-11 PMID: 3015416
  8. Transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques.
    Cell. 1989 Dec 1;59(5):847-57 PMID: 2574076
  9. Hoxb-4 (Hox-2.6) mutant mice show homeotic transformation of a cervical vertebra and defects in the closure of the sternal rudiments.
    Cell. 1993 Apr 23;73(2):279-94 PMID: 8097432
  10. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene.
    Science. 1992 May 1;256(5057):668-70 PMID: 1350108
  11. Beta 2-microglobulin deficient mice lack CD4-8+ cytolytic T cells.
    Nature. 1990 Apr 19;344(6268):742-6 PMID: 2139497
  12. Paradoxical shortening of scrapie incubation times by expression of prion protein transgenes derived from long incubation period mice.
    Neuron. 1991 Jul;7(1):59-68 PMID: 1676894
  13. The prion protein gene: a role in mouse embryogenesis?
    Development. 1992 May;115(1):117-22 PMID: 1353438
  14. Spontaneous neurodegeneration in transgenic mice with mutant prion protein.
    Science. 1990 Dec 14;250(4987):1587-90 PMID: 1980379
  15. Different scrapie-associated fibril proteins (PrP) are encoded by lines of sheep selected for different alleles of the Sip gene.
    J Gen Virol. 1991 Oct;72 ( Pt 10):2411-7 PMID: 1681027
  16. Post-mortem immunodiagnosis of scrapie and bovine spongiform encephalopathy.
    J Virol Methods. 1989 Apr-May;24(1-2):215-21 PMID: 2569471
  17. Cloning of the active thymidine kinase gene of herpes simplex virus type 1 in Escherichia coli K-12.
    Proc Natl Acad Sci U S A. 1979 Aug;76(8):3755-9 PMID: 226978
  18. Three hamster species with different scrapie incubation times and neuropathological features encode distinct prion proteins.
    Mol Cell Biol. 1990 Mar;10(3):1153-63 PMID: 2406562
  19. An in-frame insertion in the prion protein gene in familial Creutzfeldt-Jakob disease.
    Brain Res Mol Brain Res. 1990 Apr;7(3):273-6 PMID: 2159587
  20. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  21. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells.
    Cell. 1987 Nov 6;51(3):503-12 PMID: 2822260
  22. Diagnosis of Gerstmann-Sträussler syndrome in familial dementia with prion protein gene analysis.
    Lancet. 1989 Jul 1;2(8653):15-7 PMID: 2567794
  23. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours.
    Nature. 1992 Mar 19;356(6366):215-21 PMID: 1552940
  24. Scrapie prion proteins are synthesized in neurons.
    Am J Pathol. 1986 Jan;122(1):1-5 PMID: 3079955
  25. Pro----leu change at position 102 of prion protein is the most common but not the sole mutation related to Gerstmann-Sträussler syndrome.
    Biochem Biophys Res Commun. 1989 Sep 15;163(2):974-9 PMID: 2783132
  26. Precise targeting of the pathology of the sialoglycoprotein, PrP, and vacuolar degeneration in mouse scrapie.
    Neurosci Lett. 1989 Jul 17;102(1):1-6 PMID: 2550852
  27. Scrapie prion protein contains a phosphatidylinositol glycolipid.
    Cell. 1987 Oct 23;51(2):229-40 PMID: 2444340
  28. A rapid method for preparing synaptosomes: comparison, with alternative procedures.
    Brain Res. 1981 Dec 7;226(1-2):107-18 PMID: 7296283
  29. Novel missense variants of prion protein in Creutzfeldt-Jakob disease or Gerstmann-Sträussler syndrome.
    Biochem Biophys Res Commun. 1993 Mar 15;191(2):709-14 PMID: 8461023
  30. Identification of a gene which controls the incubation period of some strains of scrapie agent in mice.
    J Comp Pathol. 1968 Jul;78(3):293-9 PMID: 4970191
  31. The scrapie fibril protein and its cellular isoform.
    Curr Top Microbiol Immunol. 1991;172:57-74 PMID: 1687385
  32. HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells.
    Nature. 1987 Mar 19-25;326(6110):292-5 PMID: 3821905
  33. Mutant prion proteins in Gerstmann-Sträussler-Scheinker disease with neurofibrillary tangles.
    Nat Genet. 1992 Apr;1(1):68-71 PMID: 1363810
  34. A cellular gene encodes scrapie PrP 27-30 protein.
    Cell. 1985 Apr;40(4):735-46 PMID: 2859120
Article Info
Journal
Molecular neurobiology
Abbr.
Mol Neurobiol
ISSN
0893-7648
DOI
10.1007/BF02780662
Published
1994-00-00
Pages
121-7
Language
English
Region
United States
NLM ID
8900963
Subset
IM
External Links
PubMed source DOI: 10.1007/BF02780662 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2