Monitoring transgenic mice

1. Monitoring transgenic mice Which lines need monitoring? 1. New lines produced by: Gene targeting or insertional transgenesis Mutagenesis, natural or induced Subsequent germ-line genetic change such as breeding to homozygosity or deletions due to action of recombinases (Cre and Flp) 3. Change of environment Assessing the welfare of GA mice: Report of GA mouse welfare assessment group. April 2006 Lab Animals 40(2), 111-114

2. Monitoring transgenic mice Which lines need monitoring? 1. New lines produced by: Gene targeting or insertional transgenesis Mutagenesis, natural or induced Subsequent germ-line genetic change such as breeding to homozygosity or deletions due to action of recombinases (Cre and Flp) 3. Change of environment All lines where a heritable genetic manipulation may have consequences for the welfare of the mouse Need for development of a welfare profile that can be shared between institutions along with the mouse line

3. Monitoring transgenic mice Who participates in monitoring? Animal technicians Veterinarians or facility managers Researchers ACEC members

4. Monitoring transgenic mice Who participates in monitoring? Animal technicians Veterinarians or facility managers Researchers ACEC members Animal technicians should be involved in welfare assessment. In-house training must be given in assessment that is: Structured Standardised Easy to learn Quick to perform Regularly reviewed

5. Monitoring transgenic mice Animal technicians Researcher Facility vet Who analyses the data? ACEC

6. Monitoring transgenic mice Animal technicians Researcher Facility vet Who analyses the data? ACEC Research investigators and facility management should determine whether welfare concerns exist for each GM line and report any concerns to ACEC. Needs establishment of benchmarks and required numbers

7. Monitoring transgenic mice What action is to be taken when deleterious phenotypes are recognised? ACEC informed of welfare concerns Researcher and facility manager work together on a management plan to minimise adverse welfare consequences Animal technicians continue to assess welfare as recommendations are implemented Necessary actions concerning relevant treatments and humane endpoints to form a welfare profile for the line

8. Monitoring transgenic mice How do deleterious genetic changes arise? Apart from desired genetic alteration, additional changes may occur: Genetic drift-spontaneous mutations occur over time Random insertion transgenics-injection of DNA into pronucleus Mechanical damage to embryo Disruption of gene at site(s) of insertion Gene targetted lines- manipulation of embryonic stem cells poor handling of es cells in culture leads to chromosome loss

9. Monitoring transgenic mice What is normal for this mouse line? The strain background used to produce the mice must be taken into consideration: C57BL/6 B6D2 F1 (C57BL/6 x DBA2) B6SJL F1 (C57BL/6 x SJL) FVBn 129 (various substrains) can be mixed, and composition unknown. What are the appropriate controls to use for growth charts behavioural differences reproductive performance susceptibility to disease Comparison to littermates is often the most meaningful control

10. Monitoring transgenic mice How can conditions be improved for the mouse? Change in housing Conventional to barrier Noise reduction Change in background strain To improve breeding performance To lessen effects of a severe phenotype Change in breeding strategies Maintaining heterozygous breeding pairs Specialist care Recognising humane end-points