The proviruses of the N-tropic, ecotropic virus (AKV) of AKR mice (Akv-1, Akv-2) have been studied by the Southern gel-filter transfer technique. These proviruses can be detected by cleavage of cell DNA by BamHI endonuclease, which-yields characteristic subgenomic DNA fragments upon cleavage of this type of provirus. Proviruses integrated into different sites in the mouse genome can be resolved with EcoRI endonuclease, which does not cleave the AKV proviruses. Use of congenic and backcrossed mice and a radioactive DNA probe enriched for AKV sequences has allowed identification of the EcoRI fragments carrying the proviruses of the genetically defined Akv-1 and Akv-2 loci. Novel proviruses introduced by superinfection of cultured AKR cells with AKV and present in leukemic cells from AKR mice have also been identified. Comparison of substrains of AKR mice indicates some heterogeneity in their spectra of proviruses.The AKR strain of mouse is characterized by a life-long expression of an ecotropic N-tropic murine leukemia virus, AKV, and a 70-95% incidence of leukemia (1, 2). Both of these characteristics are the result of dominant alleles present at two loci, Akv-1 and Akv-2 (3). Congenic mice have been constructed that possess either the Akv-1 or Akv-2 allele in the genetic background of the NIH/Swiss strain of mouse (4), a strain which otherwise lacks such alleles. Hybridization of DNA from such congenic mice to an AKV cDNA probe demonstrated that the Akv-1 allele segregates with and presumably represents a provirus for AKV. The allele at Akv-2 is associated with a second, apparently identical (5), provirus.The proviruses present at Akv-1 and Akv-2 are not necessarily expressed. Embryonic AKR mice and many cell lines derived from AKR embryos do not produce virus. In vitro, expression of virus occurs at a low frequency spontaneously and at a much higher frequency upon induction with BrdUrd (6). Because AKR cells are sensitive to exogenous infection with AKV, such transient induction of virus expression leads to horizontal infection of the entire culture and subsequent continuous virus production. In vivo, expression of virus occurs from some cells in all postnatal AKR mice. The in vivo expression of virus is probably also the result of transient induction of virus by a few cells followed by horizontal infection of other cells in the animal.The number of AKV proviruses present in virus-negative, virus-producing, and leukemic AKR cells has been estimated by liquid hybridization (7,8). This technique allows relatively accurate quantitation of the amount of AKV sequences present in a given DNA sample. It provides no information, however, about the organization of these sequences. Recently, the Southern gel-filter transfer technique (9) has been used successfully to analyze single integrated murine leukemia virus (MuLV) proviruses in rodent cells (10). We apply this technique here to identify the Akv-1 and Akv-2 genetic loci with specific DNA fragments produced by restriction endonucleases, to identify specific ...

Neuroethics, a recently modernized field at the intersection of bioethics and neuroscience, is founded on centuries of discussion of the ethical issues associated with mind and behavior. Broadly defined, neuroethics is concerned with ethical, legal and social policy implications of neuroscience, and with aspects of neuroscience research itself. Advances in neuroscience increasingly challenge long-held views of the self and the individual's relationship to society. Neuroscience also has led to innovations in clinical medicine that have not only therapeutic but also non-therapeutic dimensions that extend well beyond previously charted boundaries. The exponential increase in cross-disciplinary research, the commercialization of cognitive neuroscience, the impetus for training in ethics, and the increased attention being paid to public understanding of science all illuminate the important role of neuroethics in neuroscience.

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A restriction endonuclease cleavage map of the genome of AKV, the endogenous, ecotropic leukemia virus of AKR mice, has been derived. By using this map and analyzing DNA from congenic mice, we have defined four DNA fragments diagnostic for AKV proviruses. Analysis of DNAs from 10 strains of American laboratory mice revealed that all strains carrying inducible, ecotropic murine leukemia viruses yielded DNAs which contained the four DNA fragments diagnostic for AKV. Virus-negative strains lacked these fragments in their DNA. Screening DNA from 23 additional mice revealed that, among these mice, only mice from Asia gave rise to the DNA fragments diagnostic of an AKV provirus. We conclude that all of the endogenous ecotropic murine leukemia proviruses in American laboratory mice are closely related since they share a common set of restriction endonuclease cleavage sites. These proviruses appear to derive from the East Asian ancestors of these mouse strains. Analysis of DNA from six selected mice with an additional restriction endonuclease showed that greater than 97% of the nucleotide sequences in each provirus are contigous and that these endogenous proviruses are indistinguishable from proviruses introduced by exogenous infection.