Faculty Research 1980 - 1989
Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time.
Document Type
Article
Publication Date
1988
Keywords
Blotting-Southern, Crosses-Genetic, Genes-Structural, Genes-Viral, Kinetics, Linkage-(Genetics), Mice, Mice-Inbred-Strains, Polymorphism-(Genetics), Prions: ge, Scrapie-Agent: ge, Species-Specificity, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Viral-Proteins: ge
First Page
5528
Last Page
5540
JAX Location
1734
JAX Source
Mol Cell Biol 1988 Dec; 8(12):5528-40.
Grant
NS14069, NS22786, GM37821
Abstract
The mouse prion protein (PrP) gene (Prn-p), which encodes the only macromolecule that has been identified in scrapie prions, is tightly linked or identical to a gene (Prn-i) that controls the duration of the scrapie incubation period in mice. Constellations of restriction fragment length polymorphisms distinguish haplotypes a to f of Prn-p. The Prn-pb allele encodes a PrP that differs in sequence from those encoded by the other haplotypes and, in inbred mouse strains, correlates with long scrapie incubation time (Westaway et al., Cell 51: 651-662, 1987). In segregating crosses of mice, we identified rare individuals with a divergent scrapie incubation time phenotype and Prn-p genotype, but progeny testing to demonstrate meiotic recombination was not possible because scrapie is a lethal disease. Crosses involving the a, d, and e haplotypes demonstrated that genes unlinked to Prn-p could modulate scrapie incubation time and that there were only two alleles of Prn-i among the mouse strains tested. All inbred strains of mice that had the Prnb haplotype were probably direct descendants of the I/LnJ progenitors. We established the linkage relationship between the prion gene complex (Prn) and other chromosome 2 genes; the gene order, proximal to distal, is B2m-II-1a-Prn-Itp-A. Recombination suppression in the B2m-Prn-p interval occurred during the crosses involved in transferring the I/LnJ Prnb complex into a C57BL/6J background. Transmission ratio distortion by Prna/Prnb heterozygous males was also observed in the same crosses. These phenomena, together with the founder effect, would favor apparent linkage disequilibrium between Prn-p and Prn-i. Therefore, transmission genetics may underestimate the number of genes in Prn.
Recommended Citation
Carlson GA,
Goodman PA,
Lovett M,
Taylor BA,
Marshall ST,
Peterson TM,
Westaway D,
Prusiner SB.
Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time. Mol Cell Biol 1988 Dec; 8(12):5528-40.