IBC Policy on Transgenic Animals

(Adopted 1/10/08)

Introduction

The purpose of this policy is to describe the Institutional Biosafety Committee (IBC) review and approval procedures required for all research activities that involve whole transgenic vertebrate animals. “Transgenic animal” is any whole vertebrate animal in which the animal's genome has been altered by stable introduction of recombinant DNA, or DNA derived there from, into the germ-line (production of transgenic animals).

If you are going to initiate any research project that is expected to generate transgenic rodents or purchase, transfer and/or generate any other whole transgenic vertebrate animal, refer to Section IV (Instructions for Compliance) of this policy.

NOTE: the purchase or transfer of commercial whole transgenic rodents is exempt from IBC review under the NIH Guidelines under Section III-D-4-c(2) and Appendix C-VI.

I.Scope

All University of Missouri Principal Investigators and research staff must comply with this policy, the National Institutes of Health (NIH), Guidelines for Research Involving Recombinant DNA Molecules (Guidelines) and all other applicable University of Missouri research policies. Research (internal and extramural funding) activities that are conducted with the goal of producing transgenic animals by use of recombinant DNA technologies described in the NIH guidelines, must be reviewed and approved by the Institutional Biosafety Committee (IBC) and the Animal Care and Use Committee (ACUC). Methods for transgenic animal production include, but are not limited to DNA microinjection, retrovirus-mediated gene transfer and embryonic stem cell mediated gene transfer. IBC review and approval also may be required for transgenic animal breeding programs on a case-by-case basis.

II. Physical and Biological Containment Levels

The containment levels required for research involving recombinant DNA associated with or in animals, is based on classification of experiments in Section III, Experiments Covered by the NIH Guidelines. For the purpose of animal research, four containment levels are established in Appendix G in the NIH Guidelines for physical containment of smaller animals: BL1, BL2, BL3 and BL4. There are also four containment levels established in Appendix Q in the NIH Guidelines for physical and biological containment of larger animals with growth requirements such as cattle, swine, sheep, goats, horses, and poultry that preclude Appendix G: BL1–Animals (N), BL2-N, BL3-N and BL4-N.

III. Experiments Involving Transgenic Rodents and Animals

The physical and biological containment levels for experiments involving Whole Transgenic Vertebrate Animals must conform to NIH Guidelines unless directed by the IBC.

A. Section III-E-3: Experiments Involving Transgenic Rodents (BL1)

“This section covers experiments involving the generation of rodents in which the animal's genome has been altered by stable introduction of recombinant DNA, or DNA derived therefrom, into the germ-line (transgenic rodents). Only experiments that require BL1 containment are covered under this section; experiments that require BL2, BL3, or BL4 containment are covered under Section III-D-4, Experiments Involving Whole Animals.”

B. Section III-D-4: Experiments Involving Whole Transgenic Animals (BL2- BL3 containment)

“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 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.”

Please note: Designations such as “whole transgenic animals” and “whole animals” include transgenic rodents for this section unless covered in Section III-E-3 “Experiments Involving Transgenic Rodents (BL1) as shown above.

“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.”

IV. Instructions for Compliance

Before initiating any research project that is expected to purchase, transfer or generate whole transgenic vertebrate animals (except purchase or transfer of whole transgenic rodents), the Principal Investigator (PI) must conduct the following steps:

1. The PI must complete an ACUC application form which will allow the ACUC to review the animal usage. This form will have a worksheet which will ask basic questions to determine if an IBC application has to be submitted. A subcommittee of the IBC (IBC Subcommittee on Transgenic Vertebrate Animals) consisting of the IBC Chair, a scientific member of the IBC, the Biosafety Professional and an ad hoc animal expert will review the worksheet to determine if the work requires a submission of an IBC application for full committee review.
2. In accordance with IBC Policy, the animal use worksheet found on the ACUC application form for animal usage must include the following information:

   a. the purpose of the project

   b. animal species

   c. transgene name

   d. transgene function

   e. transgene source

   f. vector(s) used

   g. method of animal transformation

   h. physical location of the laboratories and research animals at the University

   i. indication if the gene encodes a toxin or other hazardous agent

   j. method of disposal

3. Based on the written information on the worksheet, the IBC Subcommittee on Transgenic Vertebrate Animals will determine the subsequent extent of institutional review. In rare instances, the project may need to be referred to the NIH Office of Biotechnology Affairs (OBA) for NIH review, e.g., use of a modified animal that may compromise agriculture, if released. In most cases, the IBC Subcommittee on Transgenic Vertebrate Animals will determine that the project will require: a. verification and registration with the IBC-work can begin following final approval by the ACUC. (full IBC review and approval IS NOT required prior to the initiation of the experiment) b. submission of an IBC application form to the IBC for review and approval. (full IBC review and approval IS required prior to the initiation of the experiment) Whole animal work can proceed in the event of the latter upon ACUC approval.
4. Before transgenic animals or their tissues can be shipped to or from the University of Missouri and scientists at other institutions or companies, the transgenic vertebrate animal application form must clearly describe the animals and/or animal tissues, and include but not be limited to, gene constructs, plasmids and genetic changes in the animals. International shipments may require special review due to export requirements.
5. When any transgenic animal is euthanized or dies, the carcass must be disposed of by incineration. The Biohazardous Unwanted Materials Program and MU Business Policies are available at the EHS and MU Business Services websites, respectively. The incineration requirement applies to transgenic animals, potentially transgenic animals, "no-takes" in the production of transgenic animals, and progeny of transgenic animals. There are no exceptions to this policy without review and written approval by the Biosafety Professional.
6. The PI is responsible for reporting the inadvertent release of transgenic animals, improper disposal of transgenic animals or other incidents in the laboratory or vivaria to the Biosafety Professional, who shall report them to the IBC, MU Attending Veterinarian and to the NIH, if deemed necessary.
7. The PI is responsible for training graduate students, teaching assistants and staff about the policies and procedures for transgenic animal handling and appropriate carcass disposal.
8. Any breeding of transgenic, non-rodent vertebrate animal species (including but not limited to sheep, cows, pigs and other large vertebrate animals) requires written application to the ACUC and subsequent review by the IBC Subcommittee of Transgenic Vertebrate Animals, who together shall discuss the appropriate review process for this category of experiments. The IBC shall refer to Appendix G and Q of the Guidelines to determine appropriate containment.
9. Any breeding of two different transgenic vertebrate animal models requires written application to the ACUC and subsequent review by the IBC Subcommittee of Transgenic Vertebrate Animals which shall discuss the appropriate review process for experiments that may produce a double knockout or other unique transgenic animal. The IBC may refer to Appendix G and Q of the NIH Guidelines as necessary to determine appropriate containment.

If there are any questions regarding this policy, please contact the Biosafety Professional at 882-7018.