Institute of Laboratory Animal Science University of Zurich

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Transgenic Mouse ModelsBio 426 / WS 2006/2007
Kurt Bürki, Institute of Laboratory Animal
Science, University of Zurich
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...The challenge with transgenic animals is no
longer technical but resides where it should, in
ones ability to ask the right question. ...
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• Models in Immunology Immunological Tolerance
• Principles of Mouse Breeding

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Inbreeding scheme
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Breeding pairs
Line pairs
Breeding line
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Inbred Strain

• Is the result of at least 20 generations of
  brother x sister mating.
• All individuals are homozygous for (almost) all
  alles.
• All individuals are (almost) genetically
  identical (isogenic).
• Offspring is genotypically identical to the
  parents.

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Resistance against Plasmodium chabaudi
Differences in survival rates when comparing
different inbred strains of the mouse
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80
70
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überlebende Mäuse
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30
20
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0
C57BL/10
B10.D2
BALB/c
BALB/b
DBA/2J
Mouse-Strain
from Infection and Immunity, Sept. 1988, p.
2400-2406
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Outcross Rotation-Breeding
Avoids brother-sister mating
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Inbred vs. Outbred
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Inbred/Outbred Nomenclature

• Inbred Strains / Lines
• eg. C57BL/6J NOD/Bom SHR/NCrl
• Reference Beck et al.
  Genealogies of mouse inbred strains.
• nature genetics 24, 23-25
  (2000).
• Outbred Stocks / Breeds
• eg. CrlNMRI HanNMRI NTacSD
• Reference The origins and uses
  of mouse outbred stocks.
• nature genetics 37, 1181-1186
  (2005).

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Problems with transgenic mice

• Undefined mixed background
• Generation of transgenic animals using hybrid
  zygotes or strain 129-derived ES cells
• Combination of different transgenic lines from
  different origin with different genetic
  backgrounds

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Reviews

• Bockamp et al. Of mice and models Improved
  animal models for biomedical research. Physiol.
  Genomics 11, 115-132 (2002)
• Rogner U.C. and Avner P. Congenic mice Cutting
  tools for complex immune disorders. Nature
  Reviews Immunology 3, 243-252 (2003).