Systematic Evaluation of the Mouse Eye: Anatomy, Pathology, and Biomethods

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Publication Date: 12/20/2001 - Complete Document

Description :


With completion of the first phase of the Human Genome Project, it is evident that scientists are confronted with mountains of information. The availability of all human genes and their locations is an exciting prospect. However, the nature of the proteins coded for by these genes and their molecular mechanisms of action are often unknown. Efforts to take advantage of this new fund of knowledge are complicated by several factors: (1) every human has a unique set of genes that make the search for cause and effect a challenging endeavor; (2) infinite variations in environment influence gene expression in humans and such factors are difficult to control; (3) gene expression in humans is difficult to study because many tissues and organs are not easily or safely accessible for biopsy; (4) tissue from diseased human organs is sometimes obtained only after years of impact from medicine, surgery, and the disease itself; and (5) many diseases are complex traits and are the result of the interaction of many genes, some of which exert modest effects; such genes are difficult to detect or map.

These problems are best addressed by mouse genetics. It is well known that 90 to 95% of the mouse and human genomes is shared. This fact makes it likely that a given gene in a mouse will be found in a homologous chromosomal segment in humans and will exert its effects through similar mechanisms. The first draft of the mouse genome is already available. The list of advantages in using mice for genetic research is long: (1) Inbred strains of mice are genetically identical except for the mutation being studied; (2) evolution of disease is more rapid in mice because of their 2- to 3-year life span; (3) diet and environment can be precisely controlled; (4) tissue is available for study early in the disease process; (5) there are many well-characterized spontaneous mutant mice available; and (6) genes can be manipulated by targeted mutagenesis.

Although numerous sophisticated techniques are available in genetics, the study of disease remains firmly linked with the disciplines of anatomy and pathology. In some tissues, structural details are relatively simple and easily interpreted. The eye, however, is an asymmetrical organ of complex structure with important regional anatomic variations. If orientation of the eye during sectioning is not carefully controlled, it is easy to make erroneous interpretations. This problem is complicated by the size of the mouse eye and the fact that the eyes of all animals are challenging tissues to fix and section without artifacts. These difficulties can be overcome by use of the techniques discussed in this book.

Our primary goals are to describe the normal anatomy, development, general pathology, and methodology for evaluation of the mouse eye and adnexae. Although this information is available in the scientific literature, it is widely scattered. Efforts have been made to provide the reader with extensive bibliographies at the close of each chapter as resources for additional information. A separate CD that contains all figures in color is included with the book, because color versions of the figures offer details not obvious in black-and-white pictures. Where needed, electron microscopic pictures illustrate features not visible with light microscopy, although this book is not intended to be a comprehensive guide to ocular ultrastructure.

The middle sections of the book review issues in mutant evaluation and the ocular histopathological features of diseases that occur in response to genetic and environmental stimuli. Space does not permit a complete review of the histopathological features of every genetically engineered mouse that has been reported; the material presented is intended to cover the general morphological changes in mice and to provide a basis for interpreting new mouse mutations. A constant effort has been made to relate human ocular disease to mouse models of disease. Chapters on mapping of complex traits and on ENU mutagenesis are included as an introduction to these important techniques and their relationship to analysis of morphology.

The final portion of the book is devoted to procedures for tissue preparation and interpretation as well as to methodology useful for examination and evaluation of the mouse eye. It is difficult to think of doing genetic research without the huge reservoir of information available online, so the final chapter describes Internet resources that provide supplementary information.

Document Type : Complete Document

Language : English

Page Count : 383

Publication Date : 12/20/2001

Revision : 01

Status : Current

Title : Systematic Evaluation of the Mouse Eye: Anatomy, Pathology, and Biomethods