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We are in a genomic revolution, and many of the major advances in applied physiology are based on discoveries made with genetic model systems. These model systems provide not only an in-depth understanding of normal human physiology but also serve as models of human disease. Because of the wealth of scientific information that is forthcoming, and because this is already impacting human health, it is imperative at this stage to pause and evaluate some of the important information that has already been provided by genetic model systems. It is also important to put in perspective some of the driving forces and limitations behind the development of new model systems for the applied physiology of the future. With the invited mini-reviews and original articles of this Highlighted Topics series, the Associate Editors and I are pleased to further promote research and publication of investigations in applied physiology that utilize genetic model systems.

In the first mini-review of this Highlighted Topics series, entitled "Identifying new mouse models of cardiovascular disease: a review of high-throughput screens of mutangenized and inbred strains," Dr. L. Peters and colleagues focus on phenotype-driven approaches for identifying genetic mechanisms underlying the pathophysiology of cardiovascular disease. The approach in this mini-review is two-pronged. First, as part of the International Mouse Phenome Project, 48 inbred strains were screened to identify the existing variation in cardiovascular phenotypes. Second, N-ethyl-N-nitrosourea-mutagenized mice were screened for new recessive mutations affecting cardiovascular function. In this mini-review, Peters et al. present several new mouse models identified to date (e.g., hypertension, obesity, hyperglycemia, dilated cardiomyopathy, and cardiac arrhythmia).

Also in this issue, in a mini-review entitled "Sleeping flies don't lie: the use of Drosophila melanogaster to study sleep and circadian rhythms," Dr. J. Hendricks reviews the role that the laboratory fruit fly, Drosophila melanogaster, has played in elucidating the molecular mechanisms of circadian rhythms. These mechanisms, and in many cases the specific molecules involved, are conserved from fruit flies to vertebrates, and this understanding is also beginning to help us learn more about both clinical sleep disorders and the molecular mechanisms of sleep.

In the May issue, in a mini-review entitled "The effect of oxygen deprivation on cell cycle activity: a profile of delay and arrest," Drs. R. Douglas and G. Haddad review 1) the major phases of the cell cycle as it is currently understood and 2) the importance of the microenvironmental oxygen concentration on cell division, growth, and cell proliferation. Also highlighted is the importance of oxygen on growth during development and on tumor cell proliferation and metastasis. Although most of these studies have been performed in Drosophila melanogaster, yeast, and C. elegans, some studies have been done on mammalian cells or human cell lines.

In the June issue, in a mini-review entitled "Functional genomics in the mouse: powerful techniques for unraveling the basis of human development and disease," Dr. C. Bogue explores the mouse as a genetic model for human development and disease. This mini-review includes a discussion of the advantages and disadvantages of using the mouse as a genetic model. This mini-review provides examples of important discoveries that have been made by studying mice and focuses on future advances in research that are possible with the mouse as a model system. The detailed work includes the developmental biology and some of the potential molecular defects in lung development and growth. Now that near-complete DNA sequences of both the mouse and human genomes are available, the next major challenge will be to determine how each of these genes function, both alone and in combination with other genes in the genome. The mouse has a long and rich history in biological research, and many consider it a model organism for the study of human development and disease. Over the past few years, incredible progress has been made in developing techniques for chromosome engineering, mutagenesis, mapping, and maintenance of mutations and identification of mutant genes in the mouse. In this mini-review, many of these powerful techniques are presented along with their application to the study of development, physiology, and disease.

In another mini-review in the June issue entitled "The HXB/BXH rat recombinant inbred strain platform: a newly enhanced tool for cardiovascular, behavioral and developmental genetics and genomics," Dr. M. Printz focuses on rat HXB-BXH recombinant inbred (RI) strains, which are the largest set of rat RI strains currently available, and discusses what has been accomplished to date with these rat models as well as their future potential. Developed in Prague and rederived into a pathogen-free colony in La Jolla, California, the HXB-BXH RI strain set has facilitated identification of a large number of quantitative trait loci (QTL) for cardiovascular and metabolic phenotypes of importance to hypertension, insulin resistance, lipid abnormalities, and related cardiovascular disorders. More recently, as shown by the Printz laboratory, these RI strains are an especially powerful rodent platform for identifying loci for numerous behavioral and stress-related traits, including QTL for the bradycardia component of the orienting response, for tachycardia and pressor components elicited by the airpuff tactile startle responses, for traits associated with elevated plus maze, for diurnal rhythms of core body temperature and other traits, and for motor traits associated with the startle response. This review discusses the importance of the recent completion of a new linkage map and set of strain distribution patterns for the RI strains by this laboratory and how this will enhance the mapping utility of these strains.

As with each of the thematic topics featured in the Highlighted Topics series of the Journal of Applied Physiology, the Associate Editors and I aim to stimulate research in what we feel are important areas of investigation. We hope that these mini-reviews in the next few months will serve to 1) draw attention to some of the important work with genetic model systems that we believe will have major impacts on human health and disease in the foreseeable future, 2) promote additional research and collaborations between biologists, physiologists, and clinicians in various fields of applied physiology, and 3) entice young investigators to delve into the potential of these model systems, which are bound to have a major impact on future research in applied physiology.