The institutions and investigators have regulatory responsibilities and requirements with respect to transgenic and knockout mice. Two local institutional regulatory bodies govern the creation and use of transgenic and knockout mice: the Institutional Animal Care and Use Committee (IACUC) and the Institutional BioSafety Committee (IBC).
Investigators are required to have an active protocol approved by their institution's IACUC for the use of the animals produced by the Case Transgenic and Targeting Facility. The Case Transgenic and Targeting Facility has an approved protocol for the production of transgenic and targeted mice and there is no need for investigators to reqest IACUC approval for the procedures that the core performs. However, investigators do need an approved protocol to cover the use of mice they receive from us. The IACUC protocol should indicate if transgenic or gene targeted mice will be generated in the course of work. Such mice also require IBC approval prior to IACUC approval. Service will not be provided unless an appropriate approved protocol is documented. The Case Transgenic and Targeting Facility notifies the CWRU IACUC of its intent to transfer of mice from the service protocol to an investigator protocol.
• Information on IACUC protocol preparation
The creation of all transgenic mice and gene targeted mice requires approval by the CWRU IBC. It is the investigator's responsibility to seek approval. The Case Transgenic and Targeting Facility cooperates with the IBC by immediately notifying the IBC of all requests for chimeras and pronuclear injections. Pronuclear injections and chimera production services will not commence until the investigator is in compliance with IBC regulations.
Gene targeting or transfection of ES cells does not require IBC approval. However, IBC approval is required if mice will be made from targeted or transfected ES cells. Transgenic and knockout mice brought here from elsewhere normally do not require approval by the IBC. However, if recombinant animals from other institutions present a potential hazard (ie, biosafety hazards greater than level 1), IACUC approval should be sought.
The IBC often approves a series of vectors as part of an experimental series at one time. However, since the IBC meets only once a month investigators requesting service are encouraged to apply for IBC approval as soon as possible.
Definitions of Biosafety Levels
Definitions of Biosafety Levels 1 to 4 from Biosafety in Microbiological and Biomedical Laboratories (BMBL) 4th Edition
"Biosafety Level 1 is suitable for work involving well-characterized agents not known to consistently cause disease in healthy adult humans, and of minimal potential hazard to laboratory personnel and the environment. The laboratory is not necessarily separated from the general traffic patterns in the building. Work is generally conducted on open bench tops using standard microbiological practices. Special containment equipment or facility design is neither required nor generally used. Laboratory personnel have specific training in the procedures conducted in the laboratory and are supervised by a scientist with general training in microbiology or a related science.
Biosafety Level 2 is similar to Biosafety Level 1 and is suitable for work involving agents of moderate potential hazard to personnel and the environment. It differs from BSL-1 in that (1) laboratory personnel have specific training in handling pathogenic agents and are directed by competent scientists; (2) access to the laboratory is limited when work is being conducted; (3) extreme precautions are taken with contaminated sharp items; and (4) certain procedures in which infectious aerosols or splashes may be created are conducted in biological safety cabinets or other physical containment equipment.
Biosafety Level 3 is applicable to clinical, diagnostic, teaching, research, or production facilities in which work is done with indigenous or exotic agents which may cause serious or potentially lethal disease as a result of exposure by the inhalation route. Laboratory personnel have specific training in handling pathogenic and potentially lethal agents, and are supervised by competent scientists who are experienced in working with these agents. All procedures involving the manipulation of infectious materials are conducted within biological safety cabinets or other physical containment devices, or by personnel wearing appropriate personal protective clothing and equipment. The laboratory has special engineering and design features.
Biosafety Level 4 is required for work with dangerous and exotic agents that pose a high individual risk of aerosol-transmitted laboratory infections and life-threatening disease. Agents with a close or identical antigenic relationship to Biosafety Level 4 agents are handled at this level until sufficient data are obtained either to confirm continued work at this level, or to work with them at a lower level. Members of the laboratory staff have specific and thorough training in handling extremely hazardous infectious agents and they understand the primary and secondary containment functions of the standard and special practices, the containment equipment, and the laboratory design characteristics. They are supervised by competent scientists who are trained and experienced in working with these agents. Access to the laboratory is strictly controlled by the laboratory director. The facility is either in a separate building or in a controlled area within a building, which is completely isolated from all other areas of the building. A specific facility operations manual is prepared or adopted. Within work areas of the facility, all activities are confined to Class III biological safety cabinets, or Class II biological safety cabinets used with one-piece positive pressure personnel suits ventilated by a life support system. The Biosafety Level 4 laboratory has special engineering and design features to prevent microorganisms from being disseminated into the environment."