Transcript Monitoring transgenic animals

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
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
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 technicians
Veterinarians or facility managers
Researchers
ACEC members
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
Monitoring transgenic mice
Who analyses the data?
Researcher
ACEC
Animal technicians
Facility vet
Monitoring transgenic mice
Who analyses the data?
Researcher
Animal technicians
Facility vet
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
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:
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Genetic drift-spontaneous mutations occur over time
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Random insertion transgenics-injection of DNA into pronucleus
Mechanical damage to embryo
Disruption of gene at site(s) of insertion
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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)
FVBn
129 (various substrains)
can be mixed, and composition unknown.
What are the appropriate controls to use for
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growth charts
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behavioural differences
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reproductive performance
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susceptibility to disease
Comparison to littermates is often the most meaningful control
Monitoring transgenic mice
How can conditions be improved for the mouse?
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Change in housing
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Change in background strain
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To improve breeding performance
To lessen effects of a severe phenotype
Change in breeding strategies
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Conventional to barrier
Noise reduction
Maintaining heterozygous breeding pairs
Specialist care
Recognising humane end-points