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Genetic interactions in induction of endogenous murine leukemia virus from low leukemic mice
Abstract:
The frequency of ecotropic murine leukemia virus (MuLV) production in cells induced with halogenated pyrimidines has been investigated in several low leukemic strains of mice. Very few BALB/c or C57BL/6 (B6) induced embryo cells produce MuLV; this low frequency increases 10 to 50 fold in cells of the BALB/c x B6 F1 hybrid. Data from back-crosses of the F1 hybrid to each parent and from BALB/c x B6 recombinant inbred strains indicate that the phenotype of enhanced MuLV production results from interaction of two unlinked loci, dominant (+/+) alleles of which are carried by either parent. Genetic tests with BALB/c x B6 recombinant inbred strains confirm this two-locus model. The loci are designated Inc-1 and Inb-1 to signify their phenotypic detection by induction and the BALB/c or B6 strain of origin, respectively. Examination of hybrids of BALB/c and of B6 with other strains indicates that strains related in pedigree to BALB/c carry Inc-1, whereas those related to B6 carry Inb-1. Identification of genetic loci that specifically interact to enhance MuLV production after exposure to halogenated pyrimidines indicates the existence of mechanisms that regulate the induction or intracellular expression of endogenous MuLV.
Insights
Two genetic loci, Inc-1 and Inb-1, interact to significantly increase ecotropic murine leukemia virus (MuLV) production in mouse cells after induction. This finding reveals key regulatory mechanisms for endogenous MuLV expression.
Area of Science:
- Virology
- Genetics
- Immunology
Background:
- Endogenous retroviruses like ecotropic murine leukemia virus (MuLV) are present in the genomes of many vertebrates.
- The induction of MuLV production by chemical agents, such as halogenated pyrimidines, offers a model to study viral gene expression.
- Low leukemic mouse strains provide a baseline for understanding genetic control over MuLV production.
Purpose of the Study:
- To investigate the genetic basis for enhanced ecotropic murine leukemia virus (MuLV) production in mouse cells.
- To identify specific genetic loci and their interactions that regulate MuLV induction.
- To understand the mechanisms controlling endogenous MuLV expression.
Main Methods:
- Induction of ecotropic murine leukemia virus (MuLV) production in embryo cells from various mouse strains and hybrids using halogenated pyrimidines.
- Genetic analysis using back-crosses of F1 hybrids to parental strains.
- Utilizing BALB/c x B6 recombinant inbred (RI) strains to confirm genetic models.
- Phenotypic analysis of MuLV production in different genetic crosses.
Main Results:
- BALB/c and C57BL/6 (B6) embryo cells show low MuLV production upon induction.
- F1 hybrids (BALB/c x B6) exhibit a 10- to 50-fold increase in MuLV production compared to parental strains.
- Genetic mapping indicates that enhanced MuLV production is controlled by two unlinked loci, Inc-1 and Inb-1.
- BALB/c strains carry the Inc-1 locus, while B6 strains carry the Inb-1 locus, with dominant alleles from each parent contributing to the enhanced phenotype.
Conclusions:
- The enhanced production of ecotropic MuLV is regulated by the interaction of two distinct genetic loci, Inc-1 and Inb-1.
- These loci play a crucial role in modulating the induction and/or intracellular expression of endogenous MuLV.
- The findings provide insights into the genetic control mechanisms governing retroviral expression in mammals.
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