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Journal of Virology, September 1999, p. 7848-7852, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Fine Mapping of the Friend Retrovirus Resistance Gene, Rfv3, on Mouse Chromosome 15

Heidi J. Super,1 Kim J. Hasenkrug,1 Stacey Simmons,1 Diane M. Brooks,1 Roberta Konzek,1 Kevin D. Sarge,2 Richard I. Morimoto,3 Nancy A. Jenkins,4 Debra J. Gilbert,4 Neal G. Copeland,4 Wayne Frankel,5 and Bruce Chesebro1,*

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 598401; Department of Biochemistry, University of Kentucky, Lexington, Kentucky 40536-00842; Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 602083; Mammalian Genetics Laboratory, ABL Basic Research Program, NCI Frederick Cancer Research and Development Center, Frederick, Maryland 217024; and The Jackson Laboratory, Bar Harbor, Maine 046095

Received 1 April 1999/Accepted 24 May 1999

Rfv3 is a host resistance gene that operates through an unknown mechanism to control the development of the virus-neutralizing antibody response required for recovery from infection with Friend retrovirus. The Rfv3 gene was previously mapped to an approximately 20-centimorgan (cM) region of chromosome 15. More refined mapping was not possible, due to a lack of microsatellite markers and leakiness in the Rfv3 phenotype, which prevented definitive phenotyping of individual recombinant mice. In the present study, we overcame these difficulties by taking advantage of seven new microsatellite markers in the Rfv3 region and by using progeny tests to accurately determine the Rfv3 phenotype of recombinant mice. Detailed linkage analysis of relevant crossovers narrowed the location of Rfv3 to a 0.83-cM region. Mapping of closely linked genes in an interspecific backcross panel allowed us to exclude two previous candidate genes, Ly6 and Wnt7b. These studies also showed for the first time that the Hsf1 gene maps to the Rfv3-linked cluster of genes including Il2rb, Il3rb, and Pdgfb. This localization of Rfv3 to a region of less than 1 cM now makes it feasible to attempt the cloning of Rfv3 by physical methods.

* Corresponding author. Mailing address: Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, 903 South 4th St., Hamilton, MT 59840-2999. Phone: (406) 363-9354. Fax: (406) 363-9286. E-mail: bchesebro{at}nih.gov.

Journal of Virology, September 1999, p. 7848-7852, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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