40 GENETIC STOCKS AND BREEDING METHODS 



I 



3. In the absence of selection, all loci have equal probabilities of becoming 

 homozygous in any one system, except those linked with a locus of interest. Thus 

 alleles with deleterious effects may also become homozygous. It is inescapable that 

 alleles with deleterious effects will be selected against in the simple act of trying to keep 

 the lines in propagation. 



4. The backcross, cross-intercross, and cross-backcross-intercross systems are not 

 only efficient means of putting mutant alleles on inbred backgrounds; they also take 

 advantage of prior inbreeding and selection of the inbred line. 



5. It is not always possible, and in some instances it may not be desirable, to put 

 a mutant allele on a standard inbred background. That is, the mutant and the avail- 

 able backgrounds may be in some way incompatible. In these cases, the systems of 

 brother-sister inbreeding with forced heterozygosis offer distinct advantages. They 

 allow the background to evolve as inbreeding progresses. The mutant may thus, so to 

 speak, select its own most favorable background from those possible out of the genetic 

 makeup of the mutant generation. 



6. A new mutation which arises in an inbred line should be perpetuated within the 

 line of origin in order to keep the new mutant and its nonmutant allele on the same 

 background. Of course, this does not preclude any outcrossing which will be necessary 

 to establish the genetic basis of the new mutation and to explore its interactions with 

 various other alleles and nonalleles. 



7. The backcross, cross-intercross, and cross-backcross-intercross systems are 

 effective means of searching for genetic differences between inbred strains. The search 

 is more likely to yield positive results if any two strains having different pheno types with 

 respect to the trait under study are also different by a relatively small number of loci 

 with discrete effects. However, the true situation cannot be known until after the 

 search has been carried out. 



8. The systems described, except random mating and brother-sister inbreeding, 

 all yield mice bearing different alleles on common inbred backgrounds. These 

 strains thus constitute the precision tools for genetic, developmental, physiologic, 

 biochemical, pathologic, behavioral, and immunologic studies. They may be used in 

 either of two ways. First, the alleles caused to segregate (the locus of interest) may be 

 chosen in advance because of their known effect on hair, pigment, blood, skeleton, 

 behavior, and so forth; thus the animals bearing the different alleles are suited for 

 studies of hair or pigment or blood or skeleton or behavior. Second, the animals 

 which differ by one allele only may be studied with a view to seeing if this one allele is 

 concerned with some seemingly unrelated property of the organism. Thus dense 

 (Dd) and dilute (dd) mice may be studied for differences in learning, radiation resist- 

 ance, or susceptibility to disease. This may be a needle-in-haystack search, but once a 

 difference is found, the genetic explanation is readily at hand. 



This second type of study may be contrasted with searching for differences between 

 inbred strains with respect to such characteristics as ability to learn, resistance to 

 irradiation, or susceptibility to disease. Such a search is almost certain to uncover 



