Hybrid mice

Definition and applications

F1 hybrid mice are produced by crossing mice of two different inbred strains. Although they are heterozygous at all loci for which their parents have different alleles, they are similar to inbred strains in that they are genetically and phenotypically uniform. As long as the parental strains exist, F1 hybrids can be generated. However, unlike the parent strains, F1 hybrids do not breed true: the F2 offspring produced by mating F1 mice all have a unique random mixture of alleles from both parental strains.

Features of F1 hybrids that make them particularly useful include the following:

  • They are genetically and phenotypically uniform.
     
  • They possess hybrid vigor (are more resistant to disease, survive better under stress, live longer, and have larger litters than do either parental strain).
     
  • They are useful as hosts for tissue transplants (e.g., tumors, skin, and ovaries) from either parental strain.
     
  • For many studies, such as those involving some deleterious mutations, radiation, behavior, and bioassays for nutrients, drugs, pathogens, and hormones, they are more viable than are the parental strains.

Using hybrids as controls

F2 hybrids may be used as physiological controls for targeted mutants (knockouts) with a mixed C57BL/6 x 129 genetic background (designated B6;129). However, because of allelic segregation in gametes of the F1 hybrid parents, the genetic backgrounds of individual C57BL/6J x 129 F2 mice vary, and they are only an approximate genetic match to the B6;129 background. Still, because they carry random combinations of alleles from the C57BL/6 and 129 genetic backgrounds, they are more appropriate controls than are mice of either parental strain. The Jackson Laboratory distributes two C57BL/6J x 129 F2 hybrids, whose primary difference is the substrain of their 129 progenitor:

  • B6129PF2/J (Stock Number 100903). Parent strains: C57BL/6J-Aw–J and 129P3/J (formerly 129/J). Suggested control for strains designated B6;129P.
     
  • B6129SF2/J (Stock Number 101045). Parent strains: C57BL/6J and 129S1/SvImJ (formerly 129S3/SvImJ). Suggested control for strains designated B6;129S.

As noted in the JAX® Mice strain data sheets, the best control for a targeted mutant is the 129 strain used to produce the ES cell line from which the mutant was derived (Simpson et al. 1997; Threadgill et al. 1997). B6129F1 hybrids are usually less appropriate than are B6129F2 hybrids because the parental alleles of F1 hybrids are not segregating as are those on a mixed B6;129 background.

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.

Threadgill DW, Yee D, Matin A, Nadeau J, Magnuson T. 1997. Genealogy of the 129 inbred strains: 129SvJ is a contaminated inbred strain. Mamm Genome 8:390-3.