Abstract
The dwarf mutant is an autosomal recessive mutation of the mouse which causes a defective development of those anterior pituitary cells responsible for the production of thyroid-stimulating hormone, growth hormone, and prolactin. These mice are thus genetically hypothyroid and provide a model system in which one can investigate the influence of thyroid hormone on the transitions of the myosin heavy chain isoforms. We have carried out a qualitative and quantitative investigation of the myosin heavy chain isoforms present at various developmental stages and following one injection of 1 microgram of thyroxine. Myosin heavy chains were identified by nondissociating gel electrophoresis, localized by indirect immunofluorescence, and quantitated by the enzyme-linked immunosorbent assay technique. We find that in skeletal muscle, the appearance of the adult fast myosin heavy chain is severely retarded, that the neonatal myosin heavy chain is never totally eliminated, and that there is an overall increase in the number of fibers containing slow myosin heavy chain. In cardiac tissue the adult phenotype is never attained and beta-cardiac myosin heavy chain remains the predominant isoform. A single injection of 1 microgram of thyroxine was sufficient to cause a slight acceleration in the appearance of the adult fast myosin heavy chain in skeletal muscle, but only after 6-8 days. However, in the cardiac muscle, one injection of thyroxine resulted in a more rapid but transient expression of the alpha-cardiac myosin heavy chain, suggesting that the mechanism of action of thyroid hormone is different in these two tissues.
Highlights
The dwarf mutant is an autosomal recessive muta- onstration of an afunctional thyroigdland with corresponding tion of the mouse which causesa defective development low levels of thyroxine [2,5,11,12,13]
In our previous study [26], a qualitative investigation was carried out on the myosin isozyme transitions that occurred during development indwarf mice. These resultsshowed that in dwarf skeletal muscle the transitionfrom neonatal to adult fast myosin is considerably retarded when compared to the corresponding transition occurring in normal (+/+ or +/dw) mousemuscledevelopment
Dwarf MouseMuscle Phenotype Changes pothyroidism results ina n increase in the numberof skeletal about 80-90 days whenoncemorebecomes the exclusive fibers containing slow myosin heavy chain and an induction myosin heavy chain
Summary
From the Departement deBiologie MoEculaire, Institut Pasteur, 25, rue du Docteur Roux, 75724 Paris, France. This mutation seems of age whereas in dwarf litter mates, the neonatal myosin to inhibit the developmental disappearanofceslow fibers that heavy chain is the predominant species ( ~ 5 5 % a)t 24 days. Distribution of the myosinisozymes in the muscle fibers was analyzed by indirect immunofluorescence as described in Ref. 17 using antibodies directed against adult fast, adultslow, and neonatal rat myosins These antibodies exhibited an equivalent reactivity for the corresponding mouse isozymes[31].Histochemical ATPase stainof fibers, usually of small diameter, that contained neonatal myosin (Fig. 2d). Thseoleus was the only muscle investigated which did not contain neonatal or adult fastmyosin (Fig 3, b and c )
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