Preface

Many investigators seem to be fascinated by the coat colors of the mammals with which they work. This seems to be the case particularly for those utilizing isogenic strains of mice, not only because such strains display widely different phenotypes, but because scientists, by definition, are an inquisitive lot and it is sometimes difficult for the uninitiated to comprehend how such phenotypes are produced. This bewilderment becomes even more apparent if the investigator happens to be involved in breeding studies and a number of attractively colored animals, quite different from the origninal stocks, appear. Thus I can recall numerous occasions when my colleagues, frequently working in areas completely unrelated to any aspect of genetics, have come to me with an attractively pigmented animal or, more likely, with a population of segregating coat color types (usually because they have not tended their animals properly and have ended up with a cage full of F₂s displaying a bunch of different colors). How, they ask, do such colors come about?

While in some cases it is easy to take chalk in hand and explain what has been going on (segregating) and why, in other cases it is virtually impossible. It is extremely difficult because while the interactions of many coat-color factors obey the simple laws of heredity and of predictable gene interactions, others do not. Thus one is faced with having to say "it is just an empirical fact that..." a statement which proves nothing other than that the empirical fact is "ignorance."

Indeed, I will always remember how one such "empirical fact" revealed my ignorance at the worst possible time — my preliminary examination for the Ph.D. In my day, prelims at the University of Chicago were conducted "one on one," i.e., each student spent one hour with each faculty member. When my turn came to spend an hour with my mentor, Professor Sewall Wright, came, I was a nervous wreck. I was not nervous because Professor Wright had a reputation for being difficult in such situations, on the contrary he is a most compassionate individual, going out of his way to make things as pleasant as they can be under such trying circumstances. I was nervous because I knew that Professor Wright was just as likely to hit me with population genetics or biometry, two areas with which I have never felt at home, as he was to spend most of the time on the inheritance of coat colors in guinea pigs. I was relieved when he looked at me and said "Silvers, what do you know about the coat-color genetics of guinea pigs?" I replied that I knew more about the colors of mice, but would do my best if he would rather talk about guinea pigs (but what a relief; guinea pigs and not mathematical equations!). He said he was going to write down a number of genotypes and I was to tell him what the animals looked like. Well we started off and I was doing splendidly, basing all my answers not on personal experience, for I had very little, but on some "book knowledge" about what each coat-color determinant was supposed to do. Finally, Professor Wright (I think with a twinkle in his eye, although I'm not sure) wrote down a genotype, looked at me, and said "Silvers, what do you think this animal looks like?" A fast calculation told me that on the basis of the performance of each allele before me should be a pale cream, and I just stated that. Professor Wright, not wanting to tell me I was stupid but at the same time wanting to impress upon me the fact that I was wrong, looked at me and said "No, Silvers, not quite. It happens to be an intense brown!" Yes, Professor Wright had caught me flat-footed. I had not worked with guinea pigs, and he happened to have chosen a genotype which didn't abide completely by the "rules."

In this book many examples of such exceptions will be noted. While, on the one hand, they can make life difficult (especially on preliminary examinations), on the other such exceptions often lead to more important rules.

How I wish I could state that the subject matter which follows will serve as s simple guide for explaining to the uninitiated the whys and wherefores of coat color inheritance. However, I have no delusions about its success as a "mouse watcher's color-guide"; for this it is not. What I do hope it accomplishes, however, is to impress upon the reader that all the basic principles of genetics — the predictable and the unpredictable interaction of simple Mendelian factors and of polygenes; the influence of specific modifiers and of the genetic background as a whole; dominance, codominance, semidominance, and epistasis, etc. — are all intimately involved in making mice the colors they are.

I am indebted to many of my colleagues who in different ways helped me during the course of this effort. To all of them I wish to express my gratitude. Special appreciation is due Tim Poole who brought me back into this pigment field and who encouraged me to embark on this endeavor; George C. McKay, Jr. and Priscilla W. Lane who, upon request, provided me with many of the colored pictures; William Fore who reproduced many of the colored slides; Paul Mortensen who did many of the drawings and helped with the photography; Rita J.S. Phillips whom I continually bothered but only because each inquiry produced so much useful information; Joan Staats who time and time again promptly supplied me with information from Mouse News Letters I did not have; Maureen Geibler who typed the final draft; Herman Chase, David Gasser, and Tim Poole who very kindly read through and commented on the final draft; and Mark Licker of Springer-Verlag who more than fulfilled his part of the bargain. I also wish to acknowledge the National Institutes of Health for supporting all of my pigment cell research and for permitting me to use my current grant (CA-18640) to help defray many of the expenses in preparing what follows. Finally, I would like most to thank my family — Abigail, Deborah, and Kent — not only for putting up with me, but for having to spend many hours listening to Francis Albert Sinatra who, in my opinion, but not theirs, made all the tedious tasks associated with this effort almost enjoyable.

Willys K. Silvers