NR ACFR
AU Carlson,G.A.; Goodman,P.A.; Lovett,M.; Taylor,B.A.; Marshall,S.T.; Peterson-Torchia,M.; Westaway,D.; Prusiner,S.B.
TI Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time.
QU Molecular and Cellular Biology 1988 Dec; 8(12): 5528-40
PT journal article
AB 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.
IN Carlson et al. stellten durch Kreuzungsexperimente fest, dass außer dem Prionprotein weitere Gene auf dem Chromosom 2 bei Scrapie-Infektionen die Inkubationszeit beeinflussen.
MH Animal; Blotting, Southern; Crosses, Genetic; *Genes, Structural; *Genes, Viral; Kinetics; Linkage (Genetics); Mice; Mice, Inbred Strains; *Polymorphism (Genetics); Prions/*genetics; Species Specificity; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Viral Proteins/*genetics
AD Jackson Laboratory, Bar Harbor, Maine 04609.
SP englisch
PO USA