This section covers experiments involving whole animals in which the animal's genome has been altered by stable introduction of recombinant DNA, or DNA derived therefrom, into the germ-line (transgenic animals) and experiments involving viable recombinant DNA-modified microorganisms tested on whole animals. For the latter, other than viruses which are only vertically transmitted, the experiments may not be conducted at BL1-N containment. A minimum containment of BL2 or BL2-N is required.
Caution: Special care should be used in the evaluation of containment conditions for some experiments with transgenic animals. For example, such experiments might lead to the creation of novel mechanisms or increased transmission of a recombinant pathogen or production of undesirable traits in the host animal. In such cases, serious consideration should be given to increasing the containment conditions.
A-4-a. Recombinant DNA, or DNA or RNA molecules derived therefrom, from any source except for greater than two-thirds of eukaryotic viral genome may be transferred to any non-human vertebrate or any invertebrate organism and propagated under conditions of physical containment comparable to BL1 or BL1-N and appropriate to the organism under study (see Section V-B, Footnotes and References of Sections I-IV). Animals that contain sequences from viral vectors, which do not lead to transmissible infection either directly or indirectly as a result of complementation or recombination in animals, may be propagated under conditions of physical containment comparable to BL1 or BL1-N and appropriate to the organism under study. Experiments involving the introduction of other sequences from eukaryotic viral genomes into animals are covered under Section III-D-4-b, Experiments Involving Whole Animals. For experiments involving recombinant DNA-modified Risk Groups 2, 3, 4, or restricted organisms, see Sections V-A, V-G, and V-L, Footnotes and References of Sections I-IV. It is important that the investigator demonstrate that the fraction of the viral genome being utilized does not lead to productive infection. A U.S. Department of Agriculture permit is required for work with plant or animal pathogens (see Section V-G, Footnotes and References of Sections I-IV).
A-4-b. For experiments involving recombinant DNA, or DNA or RNA derived therefrom, involving whole animals, including transgenic animals, and not covered by Sections III-D-1, Experiments Using Human or Animal Pathogens (Risk Group 2, Risk Group 3, Risk Group 4, or Restricted Agents as Host-Vector Systems), or III-D-4-a, Experiments Involving Whole Animals, the appropriate containment shall be determined by the Institutional Biosafety Committee.
A-4-c. Exceptions under Section III-D-4, Experiments Involving Whole Animals
A-4-c-(1). Experiments involving the generation of transgenic rodents that require BL1 containment are described under Section III-E-3, Experiments Involving Transgenic Rodents.
A-4-c-(2). The purchase or transfer of transgenic rodents is exempt from the NIH Guidelines under Section III-F, Exempt Experiments (see Appendix C-VI, The Purchase or Transfer of Transgenic Rodents).