Genetic Control of Prion Incubation Period in Mice

  1. Greg Bock Organizer and
  2. Joan Marsh
  1. George A. Carlson1,
  2. David Westaway2,
  3. Patricia A. Goodman2,
  4. Marilyn Peterson2,
  5. Susan T. Marshall1 and
  6. Stanley B. Prusiner2

Published Online: 28 SEP 2007

DOI: 10.1002/9780470513613.ch6

Ciba Foundation Symposium 135 - Novel Infectious Agents and the Central Nervous System

Ciba Foundation Symposium 135 - Novel Infectious Agents and the Central Nervous System

How to Cite

Carlson, G. A., Westaway, D., Goodman, P. A., Peterson, M., Marshall, S. T. and Prusiner, S. B. (2007) Genetic Control of Prion Incubation Period in Mice, in Ciba Foundation Symposium 135 - Novel Infectious Agents and the Central Nervous System (eds G. Bock and J. Marsh), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470513613.ch6

Author Information

  1. 1

    The Jackson Laboratory, Bar Harbor, Maine 04609, USA

  2. 2

    Departments of Neurology and of Biochemistry and Biophysics, University of California, San Francisco, California 94143, USA

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471915126

Online ISBN: 9780470513613

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Keywords:

  • genetic control;
  • prion incubation period;
  • mice;
  • scrapie agent;
  • informational macromolecule

Summary

The prion gene complex (Prn) is located on mouse chromosome 2 between the beta-2-microglobulin (B2m) and agouti (A) genes. Within this complex are the prion protein gene (Prn-p), which encodes the only identified macromolecule (PrP) that purifies with infectious scrapie agent, and a scrapie incubation time gene (Prn-i). Using a variety of restriction endonucleases, six allelic forms of the Prn-p gene have been distinguished by their patterns of restriction fragment length polymorphisms. We had previously shown that the exceptionally long scrapie incubation period of I/LnJ mice inoculated with the Chandler isolate (over 200 days) was due to the effects of a scrapie incubation time gene tightly linked to Prn-p. So far, this long scrapie incubation time allele has been found only in those inbred mouse strains (I/LnJ, P/J and IM) that have the b allele of Prn-p. It is not known whether the incubation time gene and prion protein gene are two distinct loci or are one and the same. Putative recombinants between the incubation time phenotype and Prn-p genotype have been observed, but this could be due to effects of other genes segregating in the population. Regardless of whether or not the incubation time and PrP genes are identical, if any differences were found in the amino acid sequences of PrP encoded by the different Prn-p alleles there would be important implications for interpretation of results on ‘strains’ of scrapie agent. It would not be necessary to invoke nucleic acid as the informational macromolecule of the scrapie agent because differences in prion ‘strains’ recovered from mice with different Prn-p genotypes need not be the result of host selection but could be due to differences in host-encoded PrP.