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Fv2 encodes a truncated form of the Stk receptor tyrosine kinase
D A Persons1, R F Paulson, M R Loyd
1Department of Experimental Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Abstract:
The Friend virus susceptibility 2 (Fv2) locus encodes a dominant host factor that confers susceptibility to Friend virus-induced erythroleukaemia in mice. We mapped Fv2 to a 1.0-Mb interval that also contained the gene (Ron) encoding the stem cell kinase receptor (Stk). A truncated form of Stk (Sf-stk), which was the most abundant form of Stk in Fv2-sensitive (Fv2ss) erythroid cells, was not expressed in Fv2 resistant (Fv2rr) cells. Enforced expression of Sf-stk conferred susceptibility to Friend disease, whereas targeted disruption of Ron caused resistance. We conclude that the Fv2 locus encodes Ron, and that a naturally expressed, truncated form of Stk confers susceptibility to Friend virus-induced erythroleukaemia.
Insights
The Friend virus susceptibility 2 (Fv2) locus in mice is determined to be the Ron gene. A truncated form of the stem cell kinase receptor (Stk) drives susceptibility to Friend virus-induced erythroleukaemia.
Area of Science:
- * Virology
- * Genetics
- * Cancer Research
Background:
- * The Friend virus susceptibility 2 (Fv2) locus controls susceptibility to Friend virus-induced erythroleukaemia in mice.
- * Previous studies localized Fv2 to a 1.0-Mb genomic interval.
Purpose of the Study:
- * To identify the gene encoded by the Fv2 locus.
- * To elucidate the mechanism by which Fv2 confers susceptibility to Friend virus.
Main Methods:
- * Genetic mapping of the Fv2 locus.
- * Analysis of stem cell kinase receptor (Stk) gene expression in resistant and susceptible mice.
- * Functional studies involving enforced expression and gene disruption of Ron and Stk.
Main Results:
- * The Fv2 locus was mapped to an interval containing the Ron gene.
- * A truncated form of Stk (Sf-stk) was highly expressed in Fv2-susceptible cells but absent in resistant cells.
- * Enforced Sf-stk expression led to susceptibility, while Ron disruption caused resistance.
Conclusions:
- * The Fv2 locus encodes the Ron gene.
- * A naturally occurring truncated Stk variant is responsible for susceptibility to Friend virus-induced erythroleukaemia.