Handbook of Mouse Auditory Research: From Behavior to Molecular Biology PDF

Preface

It has been almost two decades since I edited The Auditory Psychobiology of the Mouse (Charles Thomas, Springfield, Illinois, 1983). That book covered the field of mouse auditory research quite adequately with only a third as many chapters as this one. Things have changed dramatically during the last two decades, and truly exciting developments have emerged in areas of molecular biology, genetics, and mouse models of human hearing disorders. Many of the topics and techniques reviewed here were not even a gleam in the eye of the authors writing in the early 1980s. But make no mistake; familiar areas of research such as auditory behavior and psychophysics, development, physiology, and anatomy have not been standing still, and equally exciting, cutting edge work is being done in these areas as well. There is a growing interest in mouse auditory phenotypes for their own sake, as well as to inform the molecular and genetic research. Fortuitously, the various disciplines fuel activity in one another. Behavioral and psychophysical research identifies the mouse models that are worthy of study at more molecular levels, whereas molecular biology helps to explain the properties of interesting auditory phenotypes. This mutual, integrative aspect of mouse auditory research is evident throughout the chapters of this book.

This book brings together as much information about these areas as is physically possible within the covers of a reasonably sized volume. The authors have done a marvelous job of presenting general background along with the current mouse research to present the state of the art of many diverse disciplines. There are always omissions in a handbook, and for those I am sorry. Every topic cannot be covered, but not many have been excluded here.

The list of contributors is close to my dream team: a mix of seasoned leaders in the field who have been well known for decades, as well as a number of rising young stars. Some of the authors were also involved with The Auditory Psychobiology of the Mouse, including John Nyby, Jim Saunders, and David Ryugo. Despite my begging, two other original contributors, Karen Steel and Guenter Ehret, were unable to write chapters this time because of other commitments. Their fine work on mice has continued over the last two decades and is well represented in various chapters.

It is hoped that the reader will come away from this handbook with an appreciation for the value and power of mouse auditory research, while being brought up to date on many topics for which mice are important subjects. We have tried to provide a mixture of reviews of the literature, current research (much of it not previously published), along with insights into the various methodologies being used. Several "focus" chapters deal with specific topics as well.

MICE AS RESEARCH ANIMALS

Of course, the use of mice in research has a long history. As reviewed recently by Pennisi (2000), it essentially began in 1664, when Robert Hooke made the first known scientific observations on mice. In 1909 Clarence Little (who would later found The Jackson Laboratory in 1929) began to develop the first inbred strain, DBA (dilute, brown, non-agouti), followed by BALB/c (Bagg albino) from 1913 to 1916, and the C57BL strain (BL = black) in 1921. Interestingly, all three of these now widely used strains possess a gene that results in progressive hearing loss, making them valuable animal models, as evidenced throughout this book. Whereas the availability of these inbred strains as models was fortunate, it has become possible to intentionally generate a variety of new models with the development of techniques to produce transgenic mice in the 1980s and knockout mice in 1987. Indeed, progress in genetic engineering of mice continues to accelerate in the 21st century, with the development of techniques that were unheard of only a few years ago.

As Davisson (1999) notes, mice have several unique advantages as animal models. First, they possess the best characterized genome of any experimental vertebrate, soon to be fully sequenced. As of 1999 about 4000 human gene homologies had already been identified and hundreds of targeted mutations had been made. Second, the variety and power of genetic techniques are unrivaled among vertebrates. Recombinant and congenic strains of various types have been produced; genes can be transferred from one genetic background to another to identify modifying genes; it is relatively easy to find polymorphic markers and phenotypic variability; sophisticated computer analysis programs are available; and others. Third, mice are practical; they are cost-efficient, easy to handle (excepting a few strains that are well known to exasperated researchers), and they reproduce rapidly. Added to this is the substantial support for mouse research provided by the NIH and other funding agencies.

The backbone of mouse research is the use of inbred strains. Many inbred strains of mice have interesting and useful auditory phenotypes themselves, but they also serve as hosts for myriad mutations and genetically engineered traits that are invaluable for auditory research. The occurrence of spontaneous mutations, and nowadays, induced-mutagenesis, provide congenic mutations that can be studied within the homogeneous inbred background. Pure-inbred strains of mice can be studied and reproducibly compared for virtually any characteristics of development, anatomy, physiology, or behavior.

Given any documented differences among the inbred strains, those strains can be crossed to produce F1 hybrids which are also genetically homogenous; that is, genetically identical except for the sex differences. All truly F1 hybrids will be either homozygous (AA or bb) or heterozygous (Cc, Dd), according to the parental inbreds. In fact, the F1 hybrids often exhibit "hybrid vigor," or advantage(s) over their respective inbred parents.

As Dr. Larry Erway (one of our contributors) notes, the greatest advantage of inbred and F1 hybrid strains of mice is that the F1 hybrids can be backcrossed to either of the parental strains for detection of: (1) equal segregation of alleles, (2) independent assortment among loci, and (3) linkage-recombination between genes. In the current age of genetic mapping, this includes some ten thousand microsatellite DNA markers closely linked among the genetic loci. Given any F1 hybrids, they can be backcrossed to either of the parent inbreds, thus the possibility of detecting equal segregation or recombination among linked genes. By crossing F1 males and females derived from the same inbred stains, the F2 progeny also provide the advantages of comparing the expression of all three genotypes (AA, Aa, aa). Potentially such comparisons can be extended to the interaction of two loci, including all nine genetic combinations: e.g., AA;BB;cc, Aa;bb;cc, and aa;Bb;cc.

As many as 25 million mice may be raised worldwide in the year 2000, accounting for more than 90% of mammals used in research (Malakooff, 2000). Whereas this is twice as many mice as were used a decade ago, the rate of use is expected to continue growing by 10 to 20% annually. Only a relatively small portion of these animals are used as subjects in research on the auditory system. However, our share of the pie is becoming larger all the time. Auditory research on mice will only continue to grow and, in all likelihood, the best is yet to come.