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Cold Spring Harbor Symposia on Quantitative Biology 02/2002; 67:409-15.
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Journal of Clinical Investigation 06/2001; 107(10):1223-5. · 15.39 Impact Factor
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ABSTRACT: In this paper, we describe the effects of voluntary cage wheel exercise on mouse cardiac and skeletal muscle. Inbred male C57/Bl6 mice (age 6-8 wk; n = 12) [corrected] ran an average of 4.3 h/24 h, for an average distance of 6.8 km/24 h, and at an average speed of 26.4 m/min. A significant increase in the ratio of heart mass to body mass (mg/g) was evident after 2 wk of voluntary exercise, and cardiac atrial natriuretic factor and brain natriuretic peptide mRNA levels were significantly increased in the ventricles after 4 wk of voluntary exercise. A significant increase in the percentage of fibers expressing myosin heavy chain (MHC) IIa was observed in both the gastrocnemius and the tibialis anterior (TA) by 2 wk, and a significant decrease in the percentage of fibers expressing IIb MHC was evident in both muscles after 4 wk of voluntary exercise. The TA muscle showed a greater increase in the percentage of IIa MHC-expressing fibers than did the gastrocnemius muscle (40 and 20%, respectively, compared with 10% for nonexercised). Finally, the number of oxidative fibers as revealed by NADH-tetrazolium reductase histochemical staining was increased in the TA but not the gastrocnemius after 4 wk of voluntary exercise. All results are relative to age-matched mice housed without access to running wheels. Together these data demonstrate that voluntary exercise in mice results in cardiac and skeletal muscle adaptations consistent with endurance exercise.
Journal of Applied Physiology 06/2001; 90(5):1900-8. · 3.75 Impact Factor
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ABSTRACT: Familial hypertrophic cardiomyopathy (FHC) is an autosomal-dominant disease that is both clinically and genetically heterogeneous. Disease-causing mutations have been found in eight genes encoding structural components of the thick and thin filament systems of the cardiac myocyte; it has therefore been coined a disease of the sarcomere. How each mutation leads to the diverse clinical phenotypes is still obscure, and research in this area is very active. Many approaches have been used to characterize the pathogenesis of the disease. Biochemical characterization of mutant alleles expressed in vitro has shed some insight into the functional deficits of several mutant alleles of myosin heavy chain, troponin-T, and alpha-tropomyosin. Transgenic animal models for FHC have been created to gain further insight into the pathogenesis of this disease. Most of these models have been made in mice; however, recently a transgenic rabbit model has been created. In addition, there are several natural-occurring forms of FHC in animals that will be interesting to explore. The discovery of additional responsible genes and the elucidation of the molecular mechanisms of pathogenesis through the use of animal models promise improved and early diagnosis and the potential for developing specific, mutation-, or mechanism-based therapeutics.
Current Opinion in Cardiology 06/2000; 15(3):189-96. · 2.33 Impact Factor
