Considerations for Choosing Controls
The most appropriate controls for mutant mouse strains can be determined by the breeding scheme used to maintain them and their genetic background.
Controls for mutants of homozygote (-/- or Tg/Tg) X homozygote (-/- or Tg/Tg) crosses
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Genetic background |
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Inbred or congenic (backcrossed for > 4 generations to an inbred strain) |
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Controls: |
inbred strain |
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Mixed background (combination of two inbred strains - e.g. B6 x 129) |
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Controls: |
F2 hybrid of parental strains (are only approximate controls—see below) |
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Complex background (3+ inbred strains, outbred or undefined background) |
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Controls: |
None |
Controls for mutant strains of heterozygote (+/-) X homozygote (-/-) crosses
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Genetic background |
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Inbred or congenic |
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Controls: |
heterozygous littermates (only if no altered phenotype) |
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Mixed background |
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Controls: |
heterozygous littermates (only if no altered phenotype) |
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Complex background |
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Controls: |
heterozygous littermates (only if no altered phenotype) |
Controls for mutant/congenic strains of heterozygote (+/-) X heterozygote (+/-) crosses
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Genetic background |
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Inbred or congenic |
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Controls: |
wildtype littermates |
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Mixed background |
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Controls: |
wildtype littermates |
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Complex background |
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Controls: |
wildtype littermates |
Controls for transgenic strains of hemizygote (Tg/+ or Tg/0) X non-carrier (+/+) crosses
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Genetic background |
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Inbred or congenic |
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Controls: |
wildtype littermates |
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Mixed background |
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Controls: |
wildtype littermates |
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Complex background |
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Controls: |
wildtype littermates |
Notes on using F2 hybrids as controls for mixed background strains
F2 hybrids should be considered only approximate controls for mixed background strains derived from two inbred strains (e.g. C57BL/6 X 129). F2 hybrid mice are generated by intercrossing the F1 hybrid offspring from crossing the two parental inbred strains. Each individual in an F2 hybrid population carries a unique combination of alleles that are segregating between the two parental strains. Within the population are individuals whose genetic background is similar to the mixed background of the mutant strain for which the F2 hybrids are to serve as controls. Depending on how many generations the mutant strain has been inbred, however, the F2 hybrid population may have more genetic diversity than that represented in the mixed background mutant population.
For mixed background strains, F1 hybrids are usually less appropriate controls than are the F2 hybrids because the parental alleles of F1 mice are not segregating (F1 hybrids are heterozygous at all loci where the inbred parental strains differ) as opposed to those in the mixed genetic background mutant mice.
We currently distribute two C57BL/6J x 129 F2 hybrids that differ in their 129 substrain progenitor:
- B6129PF2/J (100903) http://jaxmice.jax.org/strain/100903.html
Parental strains: C57Bl/6J-Aw-J and 129P3/J (formerly 129/J)
Suggested control for mixed background strains designated B6;129P - B6129SF2/J (101045) http://jaxmice.jax.org/strain/101045.html
Parental strains: C57BL/6J and 129S1/SvImJ (formerly 129S3/SvImJ)
Suggested control for mixed background strains designated B6;129S
References
Simpson EM, Linder CC, Sargent EE, Davisson MT, Mobraaten LE, Sharp JJ. 1997. Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice. Nat Genet 16:19-27.