BACKGROUND

Genetically-modified animals (GMA) have induced mutations that are human-made alterations in their genetic code. This includes both transgenic and targeted mutations that are created to study the expression, overexpression, or underexpression of a specific gene. The Guide for the Care and Use of Laboratory Animals (the Guide, NRC 2011) states: "With their inherent potential for unanticipated phenotypes, GMAs are an example of models for which increased monitoring for unexpected outcomes could be implemented." (p. 28)

IACUC Guidelines

Protocols that utilize GMA should address several items.

1. The effect that the genetic modification will have on the health of the animal must be described in detail. If this is a new modification and the health effects are unknown, describe the likely health outcomes of the genetic change according to current understanding of the gene in question and the disease state under study.
2. Endpoints to address adverse health effects
   1. The PI must provide general humane endpoints in case a severe debilitating phenotype develops and should provide the IACUC with this information in writing when the new mutant has been developed or at the next annual review of the animal-use protocol.
   2. Endpoints are relevant both in the context of experimental procedures and with regard to the potential pain or distress that is caused by the genetic modification itself.
   3. The protocol should include endpoints for the initial phase of the study when the phenotype of a new genetic modification is being characterized, as well as for later phases of the study for both experimental and non-experimental (i.e. breeding) animals.
3. Animal number estimates
   1. Should include all animals generated to produce mice of desired genotype (including culled mice of incorrect genotype and new/additional breeders to maintain colony).
4. Institutional Biosafety Committee (IBC) considerations, such as:
   1. Function of the wild type gene being inserted or the biological effect of the silenced, or knocked-out, gene.
   2. Risk(s) associated with the GMA that may create a greater hazard for research and DLAR staff
   3. If two GMA's are being bred on-site, what is the expected biological outcome of the novel strain

Please contact the IBC regarding research that includes:

1. Use of transgenic animals, except rodents
2. Creation of transgenic animals at Wayne State University, including rodents
3. Breeding of two different lines of transgenic rodents that is not exempt from the NIH Guidelines
   1. This exemption covers the breeding of two different lines of transgenic rodents, or the breeding of a transgenic rodent and non-transgenic rodent, with the intent of creating a new line of transgenic rodent that can be housed at ABSL-1 if:
      1. Both parental rodents can be housed under BSL1 containment; and
      2. Neither parental transgenic rodent contains the following genetic modifications:
         1. Incorporation of more than one-half of the genome of an exogenous eukaryotic virus from a single family of viruses; or
         2. Incorporation of a transgene that is under the control of a gammaretroviral long terminal repeat (LTR); and the transgenic rodent that results from this breeding is not expected to contain more than one-half of an exogenous viral genome from a single family of viruses.

Newly developed GMA that have not previously been characterized must be closely scrutinized for general health and behavioral abnormalities that may impact the animal's well-being.

Many GMA have already been developed and characterized. For animals with a known phenotype, a maximum holding period should be set to avoid the development of predictable problems in strains of mice that have debilitating phenotypes.

Approved: December 2012

Revision Approved: October 2017

Reviewed: April 2020