326 BIOCHEMICAL GENETICS 



tedious process. The incorporation of a dominant or semidominant color factor on a 

 uniform genetic background requires repeated backcrossing of the mutant phenotype 

 into the desired isogenic background. To replace a dominant gene with a recessive 

 gene on the same background it is necessary to alternate backcrossing with inbreeding 

 in order to recover the desired recessive character. This system of mating is described 

 by Snell 1238 for the production of isogenic resistant lines. For example, if one wishes 

 to establish albino (cc) animals coisogenic with C57 Black (CC) this is accomplished as 

 follows: First of all, the albino is mated with a C57 Black. All the offspring from such 

 a mating will be black, of course, although all will be heterozygous at the C locus (Cc) . 

 The albino phenotype is then recovered by inbreeding these heterozygous animals (one- 

 fourth will be albino) which are then backcrossed to C57 Black and so forth. With 

 each backcross generation the number of foreign factors (that is, not C57 Black) is 

 reduced by half, so that after about ten such backcrosses, albino animals are produced 

 which are essentially identical or isogenic with strain C57 Black except with respect to 

 the C locus. 



It must be emphasized that the rigorous breeding procedures essential for the 

 production of coisogenic stocks cannot be relaxed once the goal of isogenicity with the 

 desired strain has been attained. In order to maintain these stocks coisogenic with 

 each other and to eliminate all risk of the occurrence of genetic heterogeneity, it is 

 necessary to continue the same procedures employed in the establishment of these 

 stocks initially. 



Utilization of coisogenic lines in studying genie interactions. — In the mouse the in- 

 corporation of specific genes concerned with melanin formation or white spotting on a 

 C57BL/6 background was initiated some years ago by Dr. Elizabeth Russell at the 

 Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine. From foundation 

 stocks of animals differing from each other with respect to only a single locus concerned 

 with pigmentation, animals can be produced in which the interactions of two or more 

 loci can be studied on a uniform genetic constitution. These are especially useful in 

 studies to elucidate the effects of alleles at the agouti locus (described in the next 

 section) on the amount of white spotting.! 



Little 799 observed a reduction in the amount of white spotting in the coats of 

 yellow mice from that in nonyellow animals when genes responsible for the production 

 of white spotting were incorporated into the same yellow (A y a) and nonyellow (aa) 

 genotypes. Since A y is lethal when homozygous, all inbred strains of yellow animals 

 must be maintained heterozygous at this locus and are, therefore, coisogenic in nature. 

 Subsequently Dunn, Macdowell, and Lebedeff 307 demonstrated that yellow acts as a 

 modifier of one form of spotting, Ww (dominant spotting, 507 ) but has no corresponding 

 effect on other forms. Although it has been shown that the agouti allelomorphs 

 yellow-bellied agouti (A w -) and black-and-tan (a 1 -), have no effect on piebald spotting 

 (ss) or its modifiers, 307 their effects on the modifiers of dominant spotting has yet to be 



f A good method of measuring quantitatively the amount of white spotting is described 

 by Russell, Lawson, and Schabtach. 1106 



