3R-Project 59-97

Phenotype characterisation and health monitoring of transgenic mice

Claudia Mertens
Zürcher Tierschutz (SPCA), 8044 Zürich, Switzerland
Thomas Rülicke
Institute of Laboratory Animal Science, University of Veterinary Medicine, 1210 Vienna, Austria.
thomas.ruelicke@vu-wien.ac.at, cmertens@zuerchertierschutz.ch

Keywords: mice; ethology: laboratory animals; ethology: transgenic animals; refinement

Duration: 1 year Project Completion: 1999

Background and Aim
When ‘creating’ new transgenic animals by genetic engineering technology or by breeding (crossing of different existing transgenic strains), it is not always possible to predict the phenotype with certainty, particularly with respect to animal welfare problems. The generation of animal models for (human) diseases often deliberately implies that the health of the animals will be compromised to some degree. The effects range from minor to lethal. To protect animal welfare and apply the criteria of the 3R, there is a need for careful phenotype monitoring and documentation of transgenic animals. Results will influence not only ethical and legal decisions surrounding transgenic strains (e.g. humane experimental endpoints, cryoconservation), but also have ramifications for breeding and maintaining transgenic animal colonies.

Method and Results
To accurately characterise phenotype, i.e. recognise and assess genetic burden or adverse effects, two steps are necessary: 1) comprehensive monitoring and documentation of a representative sample of individual animals in the sense of "life histories", and 2) the characterisation of a strain as a whole, including: i) reproduction data at the population level, ii) statistical frequency of health problems and mean age of their occurrence, iii) differences between hetero-/ hemizygote and homozygote genotypes, iv) between males and females.
Two protocols have been developed to carry out this phenotypic characterisation with mice. They are available on the web at the following site: www.bzl.unizh.ch. They include 1) score sheets for individual and litter-wise phenotype and health monitoring (from birth until spontaneous death or euthanasia), and 2) an extensive and comprehensive form for the strain characterisation. The latter is subdivided into basic and detailed information. It can be kept up to date continuously in the form of a computerised database, incorporating growing knowledge and experience of the strain, beginning with the first two generations (F1, F2) of a new strain

Conclusions and Relevance for 3R
The idea of the authors is that transgenic animals, whether commercially distributed or transferred to new facilities, should always be accompanied by their score sheet and strain characterisation form. It is hoped that the newly created forms will have an impact on the procedures in use in Switzerland since 1998 as part of the current legislative programme for a standardised documentation and characterisation of genetically modified vertebrates (Bundesamt für Veterinärwesen 1998, Switzerland). The drawbacks of the presently used form are that it mainly serves official purposes (i.e. statistics) and asks for phenotype deviations from the ‘normal’ in only a very broad manner.

References
1) The forms can be printed out from: www.bzl.unizh.ch (Tierarten-Mäuse-Formulare-Transgene Tiere-Datenerfassungsformular.pdf or Charakter-isierung.pdf).

2) Mertens C. and T. Rülicke (1999) Score sheets for individual monitoring of transgenic mice. Animal Welfare, 8; 433-438.

3) Rülicke T. and Mertens C (1999) Assessing transgenic animals: implications for animal welfare and experimental data. Der Tierschutzbeauftragte 2; 111-115.

3) Mertens C. and T. Rülicke (1999) Phenotype characterization and health monitoring of transgenic mice: a photo documentation, ATLA 27, p. 385 (Abstract).

4) Mertens C. and T. Rülicke (2000) Umfassendes Formular zur strukturierten Charakterisierung gentechnisch veränderter Tierlinien. ALTEX 17, 1/00; 15 - 21.

5) Mertens C and T. Rülicke (2000) Phänotypische Charakterisierung und Gesundheitsmonitoring transgener Tiere. Tierlaboratorium 22; 36-47.

6) Mertens C. and T. Rülicke (2000) Phenotype characterization and welfare assessement of transgenic rodents (mice). J. Appl. Welfare Science 3 (2); 127-139.