Date of Award

1985

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Abstract

The BIO 14.6 line of Syrian hamsters has been a useful model system for Duchenne dystrophy since its introduction (Homburger et al., 1962b). To reduce the effects of genetic background in this model system, a control line ('BC') was produced which shares >90% of its genotype with the BIO 14.6 line. These control animals did not differ from random-bred ('RB') control hamsters under the investigative techniques used here.;In this study, stress fibres in cultured fibroblast-like cells from muscle and skin were examined by direct staining and by indirect immunofluorescence using antibodies to the muscle proteins (alpha)-actinin, tropomyosin and M-line protein. No consistent differences in stress fibre patterns were seen among cells derived from RB, BIO 14.6, carrier and BC animals.;Organisms and cells across a broad phylogenetic range respond to a brief elevation in temperature by the new or enhanced synthesis of 'heat-shock proteins' (hsps), which are believed to serve a thermoprotective function. Changes in the cytoskeletal elements in heat-shocked cells have also been reported (Falkner et al., 1981; Thomas et al., 1981). Cultured fibroblasts from RB, BIO 14.6 carrier and BC animals showed synthesis of two hsp groups in response to temperatures above 42(DEGREES)C: a 64 kd doublet (pIs 5.8 and 5.4) and a 25 kd triplet (pIs 6.2, 5.8 and 5.4). These proteins did not show association with the nucleus under the conditions described here. Heat-shock treatment of RB-derived cells induced a change in cytoskeletal morphology; such a change was not seen in BIO 14.6-derived cells.;Antibodies were produced which recognize a 52 kd protein distinct from desmin. These antibodies stained the Z-line when used for immunofluorescence analysis of myofibrils. In preparations from dystrophic animals, however, some myofibrils showed diffuse background staining with conspicuous 'blank' regions at the Z-line. Abnormal Z-line staining was not seen in preparations from younger (7-10 day) dystrophic animals.;Myofibrils from 7-10 day animals frequently showed a fluorescent doublet in the I-Z region. The significance of the developmental shift in the distribution of the 52 kd protein is not clear at this time.

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