Monitoring transgenic mice
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Monitoring transgenic mice Which lines need monitoring? 1. New lines produced by: Gene targeting or insertional transgenesis Mutagenesis, natural or induced 2. 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
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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) - PowerPoint PPT Presentation
Transcript of Monitoring transgenic mice
Monitoring transgenic mice
Which lines need monitoring?
1. New lines produced by:Gene targeting or insertional transgenesisMutagenesis, natural or induced
2. Subsequent germ-line genetic change such as breeding to homozygosityor 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
Monitoring transgenic mice
Which lines need monitoring?
1. New lines produced by:Gene targeting or insertional transgenesisMutagenesis, natural or induced
2. Subsequent germ-line genetic change such as breeding to homozygosityor 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
Monitoring transgenic mice
Who participates in monitoring?
Animal techniciansVeterinarians or facility managersResearchersACEC members
Monitoring transgenic mice
Who participates in monitoring?
Animal techniciansVeterinarians or facility managersResearchersACEC members
Animal technicians should be involved in welfare assessment.
In-house training must be given in assessment that is:StructuredStandardisedEasy to learnQuick to performRegularly reviewed
Monitoring transgenic mice
Who analyses the data? Animal technicians
Researcher Facility vet
ACEC
Monitoring transgenic mice
Who analyses the data?
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
Animal technicians
Researcher Facility vet
ACEC
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
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
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)FVBn129 (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
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
