234 PHYSIOLOGIC GENETICS 



which is the experimenter's purpose. If one intends to analyze the effects of the 

 teratogen in relation to a variety of other factors such as developmental stage, dosage, 

 and maternal physiology, relatively large numbers of embryos will be required for the 

 appropriate statistical analyses. One of the small laboratory rodents may therefore be 

 chosen, since they are relatively economical to house and maintain, and have relatively 

 large litters. Of course, it is necessary to choose a species that responds in the desired 

 way to the teratogen (one cannot study cortisone-induced cleft palate in the rat, for 

 instance) . It may also be useful to study the interaction of genotype with teratogen, in 

 which case mice have the advantages of being genetically well known and available in 

 a variety of highly inbred lines. 



The use of inbred lines has many advantages. For embryologic studies it may be 

 worth while to search for a strain in which the teratogen to be used produces a high 

 frequency of the malformation to be studied. It also removes the variable of genetic 

 heterogeneity. Some workers 1118 have made use of F 1 hybrids between different 

 inbred strains, thus obtaining genetically uniform embryos with the additional ad- 

 vantages of hybrid vigor. The study of differences between inbred strains and crosses 

 between them in response to a teratogen is a useful way of analyzing the interaction of 

 genotype and environment in producing malformations. The existence of strains in 

 which a particular malformation occurs spontaneously in some animals provides an 

 opportunity to study the interaction of genotype and intra-uterine variables that 

 determine why some animals in a litter are affected and others not. 



Workers who are mainly interested in the pathogenesis of malformations may 

 choose a species the embryology of which is well known, or in which the embryos are 

 relatively large, permitting gross anatomic as well as microscopic study. Still others 

 may wish to produce malformations in order to study their diagnosis or treatment, in 

 which case a large species such as dog, sheep, or monkey would be advantageous. It 

 might be useful, for instance, to produce puppies with congenital malformations of the 

 heart and great vessels, to be used for improving the techniques of diagnosis and surgery 

 of such conditions, but this sort of application of experimental teratology has so far not 

 been exploited. 



Fowls, amphibia, insects, and other groups have their own special advantages for 

 teratologic work, not the least of which is the fact that embryos can be treated directly, 

 without the complication of a uterine barrier, but consideration of these lies beyond 

 the scope of this article. 



CONTROLS 



Although it should not be necessary to discuss the necessity of proper controls for 

 any experiment, some of the variables that can confuse the issue in teratologic studies 

 are sometimes overlooked and will therefore be mentioned here. 



First, there is the fact that spontaneous malformations do occur in laboratory 

 animals, and these must be distinguished from those resulting from the teratogen being 



