International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

G6. Genetic Control of Cardiorespiratory Homeostasis

J.H. Nadeau, A. Hill, S. Gerson, B. Hoit, K. Strohl, J. Singer and E.S. Lander
Departments of Genetics and Medicine, Case Western Reserve University School of Medicine, Cleveland, and Center for Genome Research, Whitehead Institute, Cambridge

Although biomedical research tends to focus on the genetics of disease, most individuals are usually healthy, despite presence of disease susceptibility genes and environmental challenges. Health, regardless of risk, implies genetic control of homeostasis that enables biological systems to accommodate challenges. As a model system, we have begun studying the genetic control of cardiorespiratory homeostatsis. Delivery of oxygen and removal of wastes requires close coordination of the cardiovascular system, respiration, hematological functions and neural controls. Our goal is to study cardiorespiratory functions as a system rather than isolated components. We surveyed the A/J and C57BL/6J strains with assays that assess cardiovascular functions (echocardiography, Doppler imaging and treadmill exercise), respiration (ventilation patterns under normal, hypoxic and hypercapnic conditions), hematology (CBC, blood chemistry), and chronobiology (heart rate, activity and temperature). Striking differences in each of these biodomains were found. The A/J and C57BL/6J strains were selected for study because they are progenitors of a panel of Chromosome Substitution Strains. The status of the B6.A-Chr(i) CSS panel as well as results for the analysis of cardiorespiratory homeostasis will be presented. These studies reveal the subtle genetic control of cardiorespiratory homeostasis as well as alternative genetic and physiological solutions to exogenous and endogenous challenges challenges.

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